|
1
|
Vargas-Castro R, García-Quiroz J, Olmos-Ortiz A, Avila E, Larrea F, Díaz L. Calcitriol prevents SARS-CoV spike-induced inflammation in human trophoblasts through downregulating ACE2 and TMPRSS2 expression. J Steroid Biochem Mol Biol 2025; 245:106625. [PMID: 39515592 DOI: 10.1016/j.jsbmb.2024.106625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 09/06/2024] [Accepted: 10/16/2024] [Indexed: 11/16/2024]
Abstract
SARS-CoV-2, the causative virus of COVID-19, increases the risk of pregnancy complications including hypertensive disorders and placental inflammation. The spike glycoprotein mediates viral cell entry by interacting with the angiotensin-converting enzyme (ACE)2 in conjunction with the transmembrane serine protease 2 (TMPRSS2). ACE1, ACE2 and renin are components of the renin-angiotensin system (RAS), which regulates blood pressure. As the placenta expresses all these proteins, it is a target for SARS-CoV-2 and a source of blood pressure modulators. Noteworthy, an ACE1/ACE2 ratio imbalance can lead to RAS dysregulation and a bad prognosis in COVID-19 patients. Calcitriol, the most active vitamin D metabolite, negatively regulates RAS, reduces inflammation, and enhances antiviral immunity, thereby protecting against COVID-19 severity. However, contrasting information exists on the regulatory role of calcitriol upon RAS components and SARS-CoV-2 receptors; while the impact of calcitriol on spike-induced inflammation in placental cells has not been explored. Thus, we studied the effects of calcitriol on these parameters using the trophoblast cell line HTR-8/SVneo and primary syncytiotrophoblasts. By RT-qPCR, ELISA, and immunocytochemistry, we found that the spike enhanced proinflammatory cytokines expression and secretion, while calcitriol significantly downregulated this effect. Calcitriol also diminished ACE1, ACE2, TMPRSS2, and renin gene expression, as well as ACE1/ACE2 mRNA ratio. CONCLUSIONS: In the human placenta, calcitriol reduced the gene expression of main RAS components and TMPRSS2, resulting in the inhibition of spike-induced inflammation. This outcome suggest that vitamin D participates in restricting SARS-CoV-2 placental infection by rendering trophoblasts less permissive to infection while helping to regulate maternal blood pressure and decreasing inflammation.
Collapse
Affiliation(s)
- Rafael Vargas-Castro
- Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Janice García-Quiroz
- Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Andrea Olmos-Ortiz
- Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Ciudad de México, Mexico
| | - Euclides Avila
- Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Fernando Larrea
- Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Lorenza Díaz
- Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico.
| |
Collapse
|
|
2
|
Secondulfo C, Visco V, Virtuoso N, Fortunato M, Migliarino S, Rispoli A, La Mura L, Stellato A, Caliendo G, Settembre E, Galluccio F, Hamzeh S, Bilancio G. Vitamin D: A Bridge between Kidney and Heart. Life (Basel) 2024; 14:617. [PMID: 38792638 PMCID: PMC11123235 DOI: 10.3390/life14050617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 04/30/2024] [Accepted: 05/09/2024] [Indexed: 05/26/2024] Open
Abstract
Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factors, such as hypertension, diabetes, obesity, and smoking, among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.
Collapse
Affiliation(s)
- Carmine Secondulfo
- Department “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
| | - Valeria Visco
- Department “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
| | - Nicola Virtuoso
- Cardiology Unit, Salerno University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy
| | - Martino Fortunato
- Cardiology Unit, Salerno University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy
| | - Serena Migliarino
- Cardiology Unit, Salerno University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy
| | - Antonella Rispoli
- Cardiology Unit, Salerno University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy
| | - Lucia La Mura
- Centro Medico Ascione Srl, 80059 Torre del Greco, Italy
| | - Adolfo Stellato
- Department “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
| | - Giuseppe Caliendo
- Department “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
| | - Emanuela Settembre
- Department “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
| | - Fabiana Galluccio
- Department of Medicine and Surgery, University of Naples “Federico II”, 80138 Napoli, Italy
| | - Sarah Hamzeh
- Department of Medicine and Surgery, University of Naples “Federico II”, 80138 Napoli, Italy
| | - Giancarlo Bilancio
- Department “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
- Nephrology Unit, Salerno University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy
| |
Collapse
|
|
3
|
ALTINTAŞ M, HİDİŞOĞLU E, CERNOMORCENCO A, ENSARİ N, SONBAY YILMAZ DN, GÜR ÖE, EYİGÖR H, GÜLMEZ ZD, BULUT E, ŞIRVANCI S, KUMRU S. Cochlear pathology in preeclamptic rats: protective effects of vitamin D and magnesium sulfate. Turk J Med Sci 2023; 53:1614-1620. [PMID: 38813514 PMCID: PMC10760567 DOI: 10.55730/1300-0144.5730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 12/12/2023] [Accepted: 10/12/2023] [Indexed: 05/31/2024] Open
Abstract
Background/aim This study investigated the possible degeneration in cochlear morphology induced by preeclampsia (PE) and the therapeutic/preventive effect of vitamin D (Vit D) and magnesium sulfate (MgSO4) used separately and together on feto-maternal outcomes. Materials and methods We created PE in rats using a reduced uterine perfusion pressure (RUPP) animal model and recorded blood pressure (BP), embryonic survival (ES), and embryonic weight (EW) and evaluated cochlear morphology by electron microscopy. Results The PE group had elevated BP, a decreased number and weight of live pups, and significant degeneration in the cochlea compared to the sham group. In the PEV group, we observed significant beneficial effects of Vit D supplementation at 14.5 and 19.5 dpc in terms of BP (p < 0.05), EW (p < 0.001), and cochlear degeneration compared to the PE group. In the PEM group, BP (p < 0.05) and cochlear degeneration nearly reached the level found in the sham group. However, although the EW was statistically different in the PE group, it did not reach sham group levels. We also observed that BP returned to sham level (p < 0.01) and noticed significant increases in the EW (p < 0.0001) and ES (p = 0.017) in the PEMV group compared to the PE group. According to the scanning electron microscope results, combined administration of VitD and MgSO4 is more effective than separate administration in improving cochlear degeneration induced by PE. Conclusion The administration of Vit D and MgSO4 during pregnancy has beneficial effects on PE pathology and may play a significant role in preventing PE-related complications, including cochlear degeneration.
Collapse
Affiliation(s)
- Mustafa ALTINTAŞ
- Department of Otorhinolaryngology, Antalya Training and Research Hospital, University of Health Science, Antalya,
Turkiye
| | - Enis HİDİŞOĞLU
- Department of Drug Science and Technology, University of Turin, Turin,
Italy
| | - Alexandra CERNOMORCENCO
- Department of Histology and Embryology, Akdeniz University Faculty of Medicine, Antalya,
Turkiye
| | - Nuray ENSARİ
- Department of Otorhinolaryngology, Antalya Training and Research Hospital, University of Health Science, Antalya,
Turkiye
| | - Didem Nevreste SONBAY YILMAZ
- Department of Otorhinolaryngology, Antalya Training and Research Hospital, University of Health Science, Antalya,
Turkiye
| | - Özer Erdem GÜR
- Department of Otorhinolaryngology, Antalya Training and Research Hospital, University of Health Science, Antalya,
Turkiye
| | - Hülya EYİGÖR
- Department of Otorhinolaryngology, Antalya Training and Research Hospital, University of Health Science, Antalya,
Turkiye
| | - Züleyha Dilek GÜLMEZ
- Department of Audiology, Faculty of Health Sciences, Istanbul University-Cerrahpasa, İstanbul,
Turkiye
| | - Erdoğan BULUT
- Department of Audiology, Faculty of Health Sciences, Trakya University, Edirne,
Turkiye
| | - Serap ŞIRVANCI
- Department of Histology and Embryology, Marmara University, İstanbul,
Turkiye
| | - Selahattin KUMRU
- Department of Obstetrics and Gynecology, Faculty of Medicine, Akdeniz University, Antalya,
Turkiye
| |
Collapse
|
|
4
|
Matias PJ, Laranjinha I, Ávila G, Azevedo A, Jorge C, Ferreira C, Aires I, Amaral T, Gil C, Ferreira A. Long-term cholecalciferol supplementation in hemodialysis patients: Effects on mineral metabolism, inflammation, and cardiac parameters. Semin Dial 2023; 36:29-36. [PMID: 35262225 DOI: 10.1111/sdi.13066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 02/13/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND Low levels of 25-hydroxyvitamin D [25(OH)D] are frequent in chronic kidney disease and are associated with adverse outcomes. The aim of this 5-year prospective study was to evaluate the effects of cholecalciferol supplementation on mineral metabolism, inflammation and cardiac parameters in hemodialysis (HD) patients. METHODS The study included 97 patients. Cholecalciferol was given after HD according to 25(OH)D baseline levels measured twice (end of winter and of summer). The 25(OH)D levels, circulating bone metabolism, inflammation parameters, brain natriuretic peptide (BNP), pulse pressure (PP), and left ventricular mass index (LVMI) were evaluated before and after supplementation. RESULTS There was a significant increase in 25(OH)D levels after supplementation (p < 0.001); however, serum calcium (p = 0.02), phosphorus (p = 0.018), and iPTH (p = 0.03) were decreased. Magnesium levels increased during the study (p = 0.03). A reduction in the number of patients under active vitamin D (p < 0.001) and in the dose and number of patients treated with darbepoetin (p = 0.02) was observed. Serum albumin increased (p < 0.001), and C-reactive protein decreased (p = 0.01). BNP (p < 0.001), PP (p = 0.007), and LVMI (p = 0.02) were significantly reduced after supplementation. CONCLUSIONS Long-term cholecalciferol supplementation allowed correction of 25(OH)D deficiency, improved mineral metabolism with less use of active vitamin D, attenuated inflammation, reduced the dose of the erythropoiesis-stimulating agent, and improved cardiac dysfunction.
Collapse
Affiliation(s)
- Patrícia João Matias
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal.,Faculdade de Ciências Médicas, NOVA Medical School, Lisboa, Portugal
| | - Ivo Laranjinha
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal
| | - Gonçalo Ávila
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal
| | - Ana Azevedo
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal
| | - Cristina Jorge
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal
| | - Carina Ferreira
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal.,Faculdade de Ciências Médicas, NOVA Medical School, Lisboa, Portugal
| | - Inês Aires
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal.,Faculdade de Ciências Médicas, NOVA Medical School, Lisboa, Portugal
| | - Tiago Amaral
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal
| | - Célia Gil
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal
| | - Aníbal Ferreira
- Dialysis Unit, Nephrocare Vila Franca de Xira, Vila Franca de Xira, Portugal.,Dialysis Unit, Dialverca, Forte da Casa, Portugal.,NIDAN, Lisbon, Portugal.,Faculdade de Ciências Médicas, NOVA Medical School, Lisboa, Portugal
| |
Collapse
|
|
5
|
Renal sympathetic denervation in resistant hypertension: The association between vitamin D and positive early response in systolic blood pressure. Rev Port Cardiol 2022; 41:311-320. [DOI: 10.1016/j.repc.2021.02.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 01/14/2021] [Accepted: 02/06/2021] [Indexed: 01/14/2023] Open
|
|
6
|
Sen A, Vincent V, Thakkar H, Abraham R, Ramakrishnan L. Beneficial Role of Vitamin D on Endothelial Progenitor Cells (EPCs) in Cardiovascular Diseases. J Lipid Atheroscler 2022; 11:229-249. [PMID: 36212746 PMCID: PMC9515729 DOI: 10.12997/jla.2022.11.3.229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 03/23/2022] [Accepted: 04/04/2022] [Indexed: 11/23/2022] Open
Abstract
Cardiovascular diseases (CVDs) are the leading cause of death in the world. Endothelial progenitor cells (EPCs) are currently being explored in the context of CVD risk. EPCs are bone marrow derived progenitor cells involved in postnatal endothelial repair and neovascularization. A large body of evidence from clinical, animal, and in vitro studies have shown that EPC numbers in circulation and their functionality reflect endogenous vascular regenerative capacity. Traditionally vitamin D is known to be beneficial for bone health and calcium metabolism and in the last two decades, its role in influencing CVD and cancer risk has generated significant interest. Observational studies have shown that low vitamin D levels are associated with an adverse cardiovascular risk profile. Still, Mendelian randomization studies and randomized control trials (RCTs) have not shown significant effects of vitamin D on cardiovascular events. The criticism regarding the RCTs on vitamin D and CVD is that they were not designed to investigate cardiovascular outcomes in vitamin D-deficient individuals. Overall, the association between vitamin D and CVD remains inconclusive. Recent clinical and experimental studies have demonstrated the beneficial role of vitamin D in increasing the circulatory level of EPC as well as their functionality. In this review we present evidence supporting the beneficial role of vitamin D in CVD through its modulation of EPC homeostasis.
Collapse
Affiliation(s)
- Atanu Sen
- Department of Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Vinnyfred Vincent
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Himani Thakkar
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Ransi Abraham
- Department of Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Lakshmy Ramakrishnan
- Department of Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| |
Collapse
|
|
7
|
Al-Ishaq RK, Kubatka P, Brozmanova M, Gazdikova K, Caprnda M, Büsselberg D. Health implication of vitamin D on the cardiovascular and the renal system. Arch Physiol Biochem 2021; 127:195-209. [PMID: 31291127 DOI: 10.1080/13813455.2019.1628064] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Vitamin D regulates the calcium and phosphorus balance in the body. The activated form of vitamin D (1 α,25-dihydroxyvitamin D) binds to vitamin D receptor which regulates genes that control cell proliferation, differentiation and apoptosis. In the cardiovascular system, the vitamin D receptor is present in cardiomyocytes and the arterial wall. A clear correlation between vitamin D level and cardiovascular diseases is established. Vitamin D deficiency affects the renin-angiotensin system leading to ventricular hypertrophy and eventually to stroke. While clinical trials highlighted the positive effects of vitamin D supplements on cardiovascular disease these still need to be confirmed. This review outlines the association between vitamin D and cardiovascular and renal disease summarising the experimental data of selective cardiovascular disorders.
Collapse
Affiliation(s)
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
- Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University, in Bratislava, Martin, Slovakia
| | - Martina Brozmanova
- Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
- Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University, in Bratislava, Martin, Slovakia
| | - Katarina Gazdikova
- Department of Nutrition, Faculty of Nursing and Professional Health Studies, Slovak Medical University, Bratislava, Slovak
- Department of General Medicine, Faculty of Medicine, Slovak Medical University, Bratislava, Slovak
| | - Martin Caprnda
- 1st Department of Internal Medicine, Faculty of Medicine, Comenius University and University Hospital, Bratislava, Slovakia
| | - Dietrich Büsselberg
- Department of Physiology and Biophysics, Weill Cornell College of Medicine, Doha, Qatar
| |
Collapse
|
|
8
|
Izzo M, Carrizzo A, Izzo C, Cappello E, Cecere D, Ciccarelli M, Iannece P, Damato A, Vecchione C, Pompeo F. Vitamin D: Not Just Bone Metabolism but a Key Player in Cardiovascular Diseases. Life (Basel) 2021; 11:life11050452. [PMID: 34070202 PMCID: PMC8158519 DOI: 10.3390/life11050452] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/03/2021] [Accepted: 05/13/2021] [Indexed: 12/12/2022] Open
Abstract
Vitamin D is the first item of drug expenditure for the treatment of osteoporosis. Its deficiency is a condition that affects not only older individuals but also young people. Recently, the scientific community has focused its attention on the possible role of vitamin D in the development of several chronic diseases such as cardiovascular and metabolic diseases. This review aims to highlight the possible role of vitamin D in cardiovascular and metabolic diseases. In particular, here we examine (1) the role of vitamin D in diabetes mellitus, metabolic syndrome, and obesity, and its influence on insulin secretion; (2) its role in atherosclerosis, in which chronic vitamin D deficiency, lower than 20 ng/mL (50 nmol/L), has emerged among the new risk factors; (3) the role of vitamin D in essential hypertension, in which low plasma levels of vitamin D have been associated with both an increase in the prevalence of hypertension and diastolic hypertension; (4) the role of vitamin D in peripheral arteriopathies and aneurysmal pathology, reporting that patients with peripheral artery diseases had lower vitamin D values than non-suffering PAD controls; (5) the genetic and epigenetic role of vitamin D, highlighting its transcriptional regulation capacity; and (6) the role of vitamin D in cardiac remodeling and disease. Despite the many observational studies and meta-analyses supporting the critical role of vitamin D in cardiovascular physiopathology, clinical trials designed to evaluate the specific role of vitamin D in cardiovascular disease are scarce. The characterization of the importance of vitamin D as a marker of pathology should represent a future research challenge.
Collapse
Affiliation(s)
- Marcello Izzo
- Department of Mathematics for Technology, Medicine and Biosciences Research Center, University of Ferrara, 44121 Ferrara, Italy
- Specialist Medical Center-Via Cimitile, 80035 Nola, Italy
- Correspondence:
| | - Albino Carrizzo
- IRCCS Neuromed, 86077 Pozzilli, Italy; (A.C.); (E.C.); (D.C.); (A.D.); (C.V.); (F.P.)
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy; (C.I.); (M.C.); (P.I.)
| | - Carmine Izzo
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy; (C.I.); (M.C.); (P.I.)
| | - Enrico Cappello
- IRCCS Neuromed, 86077 Pozzilli, Italy; (A.C.); (E.C.); (D.C.); (A.D.); (C.V.); (F.P.)
| | - Domenico Cecere
- IRCCS Neuromed, 86077 Pozzilli, Italy; (A.C.); (E.C.); (D.C.); (A.D.); (C.V.); (F.P.)
| | - Michele Ciccarelli
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy; (C.I.); (M.C.); (P.I.)
| | - Patrizia Iannece
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy; (C.I.); (M.C.); (P.I.)
| | - Antonio Damato
- IRCCS Neuromed, 86077 Pozzilli, Italy; (A.C.); (E.C.); (D.C.); (A.D.); (C.V.); (F.P.)
| | - Carmine Vecchione
- IRCCS Neuromed, 86077 Pozzilli, Italy; (A.C.); (E.C.); (D.C.); (A.D.); (C.V.); (F.P.)
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy; (C.I.); (M.C.); (P.I.)
| | - Francesco Pompeo
- IRCCS Neuromed, 86077 Pozzilli, Italy; (A.C.); (E.C.); (D.C.); (A.D.); (C.V.); (F.P.)
| |
Collapse
|
|
9
|
Soh V, Tan SJX, Sehgal R, Shirke MM, Ashry A, Harky A. The Relationship Between Vitamin D Status and Cardiovascular Diseases. Curr Probl Cardiol 2021; 46:100836. [PMID: 33848960 DOI: 10.1016/j.cpcardiol.2021.100836] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 03/08/2021] [Indexed: 12/14/2022]
Abstract
With cardiovascular conditions being a leading cause of mortality and morbidity globally, several studies have identified that there is an important correlation between the level of Vitamin D and cardiovascular diseases, including an increased risk of hypertension, heart failure, and coronary artery diseases. Current published studies are in the form of both in vivo and in vitro studies and they primarily showed the evidence of how Vitamin D can downregulate Renin-Angiotensin-Aldosterone system activity and therefore providing a cardioprotective role. Nevertheless, most of these studies are observational, and there yet to be large-scale randomized controlled trials which would increase the evidence of the findings.This review aims to capture the current evidence of Vitamin D as a metabolite which is critical in reducing cardiovascular conditions and the possible physiological pathways that it works via.
Collapse
Affiliation(s)
- Vernie Soh
- Department of Medicine, Queen's University Belfast, School of Medicine, Belfast, UK
| | - Shawn Jia Xiang Tan
- Department of Medicine, Queen's University Belfast, School of Medicine, Belfast, UK
| | - Rijuvani Sehgal
- Department of Medicine, Queen's University Belfast, School of Medicine, Belfast, UK
| | - Manasi Mahesh Shirke
- Department of Medicine, Queen's University Belfast, School of Medicine, Belfast, UK
| | - Amr Ashry
- Department of Paediatric Cardiac Surgery, Alder Hey Children Hospital, Liverpool, UK; Department of Cardiothoracic Surgery, Assiut University Hospital, Assiut, Egypt
| | - Amer Harky
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, UK; Department of Cardiothoracic Surgery, Liverpool Heart and Chest Hospital, Liverpool, UK.
| |
Collapse
|
|
10
|
Magavern EF, Warren HR, Ng FL, Cabrera CP, Munroe PB, Caulfield MJ. An Academic Clinician's Road Map to Hypertension Genomics: Recent Advances and Future Directions MMXX. Hypertension 2021; 77:284-295. [PMID: 33390048 DOI: 10.1161/hypertensionaha.120.14535] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
At the dawn of the new decade, it is judicious to reflect on the boom of knowledge about polygenic risk for essential hypertension supplied by the wealth of genome-wide association studies. Hypertension continues to account for significant cardiovascular morbidity and mortality, with increasing prevalence anticipated. Here, we overview recent advances in the use of big data to understand polygenic hypertension, as well as opportunities for future innovation to translate this windfall of knowledge into clinical benefit.
Collapse
Affiliation(s)
- Emma F Magavern
- From the William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom
| | - Helen R Warren
- From the William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom
| | - Fu L Ng
- From the William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom
| | - Claudia P Cabrera
- From the William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom
| | - Patricia B Munroe
- From the William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom
| | - Mark J Caulfield
- From the William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom
| |
Collapse
|
|
11
|
Biesalski HK. Vitamin D deficiency and co-morbidities in COVID-19 patients – A fatal relationship? NFS JOURNAL 2020. [PMCID: PMC7276229 DOI: 10.1016/j.nfs.2020.06.001] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
|
|
12
|
Hu C, Wu X. Effect of Vitamin D Supplementation on Vascular Function and Inflammation in Patients with Chronic Kidney Disease: A Controversial Issue. Ther Apher Dial 2019; 24:265-274. [PMID: 31400089 DOI: 10.1111/1744-9987.13428] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 08/06/2019] [Accepted: 08/08/2019] [Indexed: 12/22/2022]
Abstract
Vitamin D deficiency is common in patients with CKD and is associated with vascular dysfunction and inflammation. In recent years, some randomized controlled trials have revealed the effect of vitamin D supplementation on vascular function and inflammation in CKD patients, but the results are inconsistent. Thus, in light of the controversy, we performed a systematic review and meta-analysis of the effect of vitamin D in patients with CKD. We searched the literature in multiple databases for clinical trials from the date of inception to December 2018. The standardized mean difference (SMD) effect size was pooled using fixed and random effects models. A total of 10 randomized controlled trials involving 579 patients were included in the meta-analysis; among these, 313 patients were treated with vitamin D, and the control group included 266 who received a placebo. This meta-analysis revealed no statistical significance in the levels of flow-mediated dilatation (SMD, 0.94; 95% CI, -0.33 to 2.21; P = 0.15); pulse wave velocity (SMD, -0.13; 95% CI, -0.38 to 0.13; P = 0.33); systolic BP (SMD, -0.04; 95% CI, -0.29 to 0.22; P = 0.77); diastolic BP (SMD, 0.01; 95% CI, -0.26 to 0.27; P = 0.97); and CRP (SMD, -0.09; 95% CI, -0.44 to 0.26; P = 0.61) between the vitamin D group and controls for patients with CKD. Short-term intervention with vitamin D was not associated with improvements in vascular function and inflammation, as measured by flow-mediated dilatation, pulse wave velocity, systolic BP, diastolic BP and CRP. This suggested that there is insufficient evidence to conclude the benefit of vitamin D supplementation on vascular function and inflammation in CKD patients.
Collapse
Affiliation(s)
- Chun Hu
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xiaoyan Wu
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, China
| |
Collapse
|
|
13
|
Wang G, Liu X, Bartell TR, Pearson C, Cheng TL, Wang X. Vitamin D Trajectories From Birth to Early Childhood and Elevated Systolic Blood Pressure During Childhood and Adolescence. Hypertension 2019; 74:421-430. [PMID: 31256718 PMCID: PMC6938578 DOI: 10.1161/hypertensionaha.119.13120] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Accepted: 05/09/2019] [Indexed: 12/17/2022]
Abstract
Vitamin D deficiency is associated with hypertension in adults. It is unknown to what degree vitamin D status in early life can affect blood pressure (BP) a decade later. This study investigated the effect of vitamin D trajectory through early life on systolic BP (SBP) in childhood. This is a prospective birth cohort study of 775 children enrolled from 2005 to 2012 and followed prospectively up to age 18 years at the Boston Medical Center, Boston, MA. Persistent low vitamin D status is defined as plasma 25(OH)D <11 ng/mL at birth and <25 ng/mL in early childhood. Elevated SBP is defined as SBP ≥75th percentile. Low vitamin D status at birth was associated with higher risk of elevated SBP at ages 3 to 18 years: odds ratio, 1.38; (95% CI, 1.01-1.87) compared to those with sufficient vitamin D. Low vitamin D status in early childhood was associated with a 1.59-fold (95% CI, 1.02-2.46) higher risk of elevated SBP at age 6 to 18 years. Persistent low vitamin D status from birth to early childhood was associated with higher risk of elevated SBP (odds ratio, 2.04; [95% CI, 1.13-3.67]) at ages 3 to 18 years. These results suggest that low vitamin D status and trajectory in early life were associated with increased risk of elevated SBP during childhood and adolescence. Our findings will help inform future clinical and public health strategies for vitamin D screening and supplementation in pregnancy and childhood to prevent or reduce risk of elevated BP across the lifespan and generations.
Collapse
Affiliation(s)
- Guoying Wang
- Department of Population, Family and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Xin Liu
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, University of Chinese Academy of Science, Chinese Academy of Sciences, Beijing, China
| | - Tami R. Bartell
- Mary Ann & J. Milburn Smith Child Health Research, Outreach and Advocacy Center, Stanley Manne Children’s Research Institute, Ann & Robert H Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA
| | - Colleen Pearson
- Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA
| | - Tina L. Cheng
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Xiaobin Wang
- Department of Population, Family and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| |
Collapse
|
|
14
|
Vatakencherry RMJ, Saraswathy L. Association between vitamin D and hypertension in people coming for health check up to a tertiary care centre in South India. J Family Med Prim Care 2019; 8:2061-2067. [PMID: 31334180 PMCID: PMC6618207 DOI: 10.4103/jfmpc.jfmpc_236_19] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 03/20/2019] [Accepted: 04/09/2019] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Vitamin D has many effects apart from its role in calcium metabolism and bone health. Vitamin D is derived from endogenous ultraviolet-B induced vitamin D synthesis in the skin, and the current high prevalence of vitamin D deficiency in India, can be attributed to lifestyle related low sunlight exposure. Identification of the vitamin D receptor (VDR) in almost all human cells, suggests a role in extra skeletal diseases. Studies have shown that vitamin D deficiency is an independent risk factor for hypertension. AIM To evaluate the association between vitamin D and hypertension in people coming for health check up to a tertiary care center in South India. MATERIALS AND METHODS Study was carried out as a cross sectional study in a tertiary care hospital in South India. Participants (520) were both males and females (337 males and 183 females), between the age group of 20-60 years attending the comprehensive health check up clinic of our hospital. STATISTICAL ANALYSIS Statistical analysis was done using IBM SPSS statistics 20.0. RESULTS Severe vitamin D deficiency was highly prevalent in people with hypertension than in people without hypertension (P value <0.001). CONCLUSION Since India is a tropical country, till recently it was believed that vitamin D deficiency and its ill effects are uncommon. But it was found that, vitamin D deficiency was highly prevalent in people with hypertension in South India, emphasizing the need of early vitamin D supplementation. Therefore, to reduce cardiovascular morbidity, early identification of vitamin D deficiency and appropriate vitamin D supplementation may be of primary importance in population, especially like ours, having high prevalence.
Collapse
Affiliation(s)
- Rose Mary J. Vatakencherry
- Department of Physiology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham University, Kochi, Kerala
| | - L Saraswathy
- Department of Physiology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham University, Kochi, Kerala
| |
Collapse
|
|
15
|
Knowledge, attitude and practice of patients attending primary care centers toward vitamin D in Kuwait. ALEXANDRIA JOURNAL OF MEDICINE 2019. [DOI: 10.1016/j.ajme.2012.02.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
|
|
16
|
Jorde R. RCTS are the only appropriate way to demonstrate the role of vitamin D in health. J Steroid Biochem Mol Biol 2018; 177:10-14. [PMID: 28483601 DOI: 10.1016/j.jsbmb.2017.05.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 05/04/2017] [Indexed: 02/07/2023]
Abstract
Despite thousands of vitamin D studies published, including hundreds of reviews and meta-analyses, it is still uncertain if supplementation with vitamin D will have positive health effects, except for the skeleton. This cannot be answered by doing more observational studies as it is impossible to control for confounding factors and reverse causality. The only way to firmly prove positive vitamin D effects is by doing the properly designed randomized controlled trials (RCTs). However, it has been difficult to show the expected positive effects by vitamin D supplementation in RCTs, which may indicate that the effects, if present must be small. On the other hand, results from Mendelian randomization studies have shown promising results at least for mortality and multiple sclerosis. In the near future, results from several large RCTs with hard endpoints will be available. If these show positive results, the main question on vitamin D and health is answered. If they turn out negative, they will be criticized for having included subjects without vitamin D deficiency, and some studies might not have used an optimal dosing regimen. New and better-designed RCTs will then be needed, but will be very hard to perform.
Collapse
Affiliation(s)
- Rolf Jorde
- Tromsø Endocrine Research Group, Institute of Clinical Medicine, UiT The Arctic University of Norway, 9037 Tromsø, Norway; Division of Internal Medicine, The University Hospital of North Norway, 9038 Tromsø, Norway.
| |
Collapse
|
|
17
|
Furuie IN, Mauro MJJ, Petruzziello S, Riechi SC, Petterle RR, Boguszewski CL, Borba VZC. Two threshold levels of vitamin D and the prevalence of comorbidities in outpatients of a tertiary hospital. Osteoporos Int 2018; 29:433-440. [PMID: 29143130 DOI: 10.1007/s00198-017-4299-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 11/02/2017] [Indexed: 10/18/2022]
Abstract
UNLABELLED This study evaluated the number of comorbidities between two normal values of 25OHD in outpatients during 1 year of 25OHD measurements. Five hundred twenty-nine outpatients were included, patients with 25OHD ≥ 20 and < 30 ng/mL had the higher number of comorbidities, suggesting that for this specific population, 25OHD ≥ 30 ng/mL would be more appropriate. INTRODUCTION : This study evaluated the comorbidities between two values of 25OHD in outpatients of a tertiary hospital. METHODS This is a cross-sectional study with measures of 25OHD in 1-year period, excluding 25OHD < 20 and > 50 ng/mL, clinical research participants, and liver disease and chronic renal failure patients. Patients were divided into two groups: group 1 (G1), 25OHD ≥ 20 and < 30 ng/mL; and group 2 (G2), 250HD ≥ 30 and ≤ 50 ng/mL. Medical records were reviewed for demographic, laboratory, and comorbidity data. RESULTS From 529 outpatients included, 319 were in G1 (53.3 ± 15.8 years, 85% women), mean 25OHD 24.8 ± 2.8 ng/mL; and 210 outpatients in G2 (56.7 ± 16.0 years, 83% women), mean 25OHD was 36.8 ± 4.8 ng/mL. G1 had the higher number of comorbidities, including altered glycemia, dyslipidemia, hypothyroidism, urinary tract diseases, arthropathy, secondary hyperparathyroidism, anemia, and neurological and psychiatric disorders. Osteoporosis and hypothyroidism were more prevalent in G2. After binary logistic regression, the variables age (OR 0.988, CI 0.97-1.00, p = 0.048), osteoporosis (OR 0.54, CI 0.36-0.80, p = 0.003), dyslipidemia (OR 1.61, CI 1.10-2.39, p = 0.015), arthropathy (OR 2.60, CI 1.40-5.10, p = 0.003), anemia (OR 15.41, CI 3.09-280.08, p = 0.008), and neurological and psychiatric diseases (OR 3.78, CI 1.98-7.88, p = 0.001) maintained significance. CONCLUSION Patients with serum 25OHD ≥ 20 and < 30 ng/mL had higher prevalence of comorbidities compared to ≥ 30 ng/mL.
Collapse
Affiliation(s)
- I N Furuie
- Universidade Federal do Paraná, Curitiba, Brazil
| | - M J J Mauro
- Universidade Federal do Paraná, Curitiba, Brazil
| | | | - S C Riechi
- Clinical Laboratory Unit, Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil
| | - R R Petterle
- Statistics Department, Universidade Federal do Paraná, Curitiba, Brazil
| | - C L Boguszewski
- Serviço de Endocrinologia e Metabologia do Hospital de Clínicas, da Universidade Federal do Paraná (SEMPR), Curitiba, PR, Brazil
| | - V Z C Borba
- Serviço de Endocrinologia e Metabologia do Hospital de Clínicas, da Universidade Federal do Paraná (SEMPR), Curitiba, PR, Brazil.
| |
Collapse
|
|
18
|
Purswani JM, Gala P, Dwarkanath P, Larkin HM, Kurpad A, Mehta S. The role of vitamin D in pre-eclampsia: a systematic review. BMC Pregnancy Childbirth 2017; 17:231. [PMID: 28709403 PMCID: PMC5513133 DOI: 10.1186/s12884-017-1408-3] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Accepted: 07/03/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The etiology of pre-eclampsia (PE) is not yet fully understood, though current literature indicates an upregulation of inflammatory mediators produced by the placenta as a potential causal mechanism. Vitamin D is known to have anti-inflammatory properties and there is evidence of an inverse relationship between dietary calcium intake and the incidence of PE. Evidence of the role of vitamin D status and supplementation in the etiology and prevention of PE is reviewed in this article along with identification of research gaps to inform future studies. METHODS We conducted a structured literature search using MEDLINE electronic databases to identify published studies until February 2015. These sources were retrieved, collected, indexed, and assessed for availability of pregnancy-related data on PE and vitamin D. RESULTS Several case-control studies and cross-sectional studies have shown an association between vitamin D status and PE, although evidence has been inconsistent. Clinical trials to date have been unable to show an independent effect of vitamin D supplementation in preventing PE. CONCLUSIONS The included clinical trials do not show an independent effect of vitamin D supplementation in preventing PE; however, issues with dose, timing, and duration of supplementation have not been completely addressed.
Collapse
Affiliation(s)
- Juhi M. Purswani
- Division of Nutritional Sciences, Cornell University, 314 Savage Hall, Ithaca, NY 14853 USA
| | - Pooja Gala
- Weill-Cornell Medical College, New York, NY USA
| | | | - Heather M. Larkin
- Division of Nutritional Sciences, Cornell University, 314 Savage Hall, Ithaca, NY 14853 USA
| | - Anura Kurpad
- St. John’s Research Institute, Bangalore, Karnataka India
| | - Saurabh Mehta
- Division of Nutritional Sciences, Cornell University, 314 Savage Hall, Ithaca, NY 14853 USA
- St. John’s Research Institute, Bangalore, Karnataka India
| |
Collapse
|
|
19
|
Baseline Vitamin D Deficiency Decreases the Effectiveness of Statins in HIV-Infected Adults on Antiretroviral Therapy. J Acquir Immune Defic Syndr 2017; 74:539-547. [PMID: 28045766 DOI: 10.1097/qai.0000000000001281] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
OBJECTIVE Vitamin D deficiency is common in HIV. Statins may increase vitamin D, and it is unknown whether vitamin D modifies the effect of statins on cardiovascular disease. DESIGN SATURN-HIV was a 96-week, randomized, placebo-controlled trial designed to evaluate the effect of rosuvastatin on immune activation and subclinical vascular disease in HIV-infected adults on antiretroviral therapy. This analysis focuses on the prespecified secondary endpoint 25-hydroxyvitamin D [25(OH)D] concentrations. METHODS Mixed effects linear modeling and analysis of variance were used to assess the rosuvastatin effect on plasma 25(OH)D concentrations over time and to determine whether baseline vitamin D modifies the rosuvastatin effect on changes in outcomes over the trial. RESULTS Hundred forty-seven adults were randomized (72 to rosuvastatin and 75 to placebo); 78% were men, 68% African American, with a mean age of 45 years. Baseline 25(OH)D concentrations were similar (overall mean 18 ng/mL) with 65% of participants below 20 ng/mL. Changes in 25(OH)D at 96 weeks were small and not significant within- or between-rosuvastatin and placebo groups. There were significant group by vitamin D status interactions for changes in low-density lipoprotein-cholesterol, proportion of patrolling monocytes expressing tissue factor (CD14dimCD16+TF+), lipoprotein-associated phospholipase A2, and common carotid artery intima media thickness at most time points. For each of these outcomes, the beneficial effects of rosuvastatin were either not apparent or attenuated in participants with 25(OH)D <20 ng/mL. CONCLUSIONS Although 25(OH)D did not change with rosuvastatin, baseline vitamin D deficiency decreased the effectiveness of rosuvastatin. Vitamin D supplementation may be warranted for deficient patients initiating statin therapy.
Collapse
|
|
20
|
Smolensky MH, Hermida RC, Portaluppi F. Circadian mechanisms of 24-hour blood pressure regulation and patterning. Sleep Med Rev 2017; 33:4-16. [DOI: 10.1016/j.smrv.2016.02.003] [Citation(s) in RCA: 116] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 02/18/2016] [Indexed: 11/16/2022]
|
|
21
|
Yang T, Xu C. Physiology and Pathophysiology of the Intrarenal Renin-Angiotensin System: An Update. J Am Soc Nephrol 2017; 28:1040-1049. [PMID: 28255001 DOI: 10.1681/asn.2016070734] [Citation(s) in RCA: 158] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
The renin-angiotensin system (RAS) has a pivotal role in the maintenance of extracellular volume homeostasis and blood pressure through complex mechanisms. Apart from the well known systemic RAS, occurrence of a local RAS has been documented in multiple tissues, including the kidney. A large body of recent evidence from pharmacologic and genetic studies, particularly those using various transgenic approaches to manipulate intrarenal levels of RAS components, has established the important role of intrarenal RAS in hypertension. Recent studies have also begun to unravel the molecular mechanisms that govern intrarenal RAS activity. This local system is under the control of complex regulatory networks consisting of positive regulators of (pro)renin receptor, Wnt/β-catenin signaling, and PGE2/PGE2 receptor EP4 subtype, and negative regulators of Klotho, vitamin D receptor, and liver X receptors. This review highlights recent advances in defining the regulation and function of intrarenal RAS as a unique entity separate from systemic angiotensin II generation.
Collapse
Affiliation(s)
- Tianxin Yang
- Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and .,Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China
| | - Chuanming Xu
- Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China
| |
Collapse
|
|
22
|
Dirks NF, Martens F, Vanderschueren D, Billen J, Pauwels S, Ackermans MT, Endert E, Heijer MD, Blankenstein MA, Heijboer AC. Determination of human reference values for serum total 1,25-dihydroxyvitamin D using an extensively validated 2D ID-UPLC-MS/MS method. J Steroid Biochem Mol Biol 2016; 164:127-133. [PMID: 26690787 DOI: 10.1016/j.jsbmb.2015.12.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Revised: 10/15/2015] [Accepted: 12/06/2015] [Indexed: 01/18/2023]
Abstract
BACKGROUND To assess a patient's vitamin D status the precursor metabolite 25-hydroxyvitamin D can be determined. However, measurement of 1,25-dihydroxyvitamin D is required when disorders of 1a-hydroxylation, extrarenal 1a-hydroxylation, or vitamin D receptor defects are suspected. METHODS The aim of this study was to determine reference values for 1,25-dihydroxyvitamin D3 and D2 using a 2D ID-UPLC-MS/MS method. RESULTS The LC-MS/MS method, able to measure picomolar concentrations of both 1,25-dihydroxyvitamin D3 and D2 in human serum, was extensively validated. Intra-assay variations were <5% and 8.5% and <7.5% and 11%, for 1,25-dihydroxyvitamin D3 and D2, respectively, over the whole dynamic range (3.1-376 and 3.1-652pmol/L). Limit of quantitation was 3.4pmol/L for both compounds. Our method correlated well with a published LC-MS/MS method (r=0.87) and with the average 1,25-dihydroxyvitamin D3 results of the vitamin D External Quality Assessment Scheme (DEQAS) determined with LC-MS/MS (r=0.93). Reference ranges, determined in 96 plasma samples of healthy volunteers were 59-159pmol/L and <17pmol/L for respectively 1,25-dihydroxyvitamin D3 and D2. The female part of the reference group showed a statistically significant decrease of 1,25-dihydroxyvitamin D3 concentrations with age. The presence of significantly higher average 1,25-dihydroxyvitamin D3 levels in premenopausal women taking oral contraceptive pills compared to postmenopausal women suggests that this effect is estrogen-related, as estrogens lead to a higher vitamin D binding protein. CONCLUSIONS The major finding of the present study is a reference interval of 59-159pmol/L for 1,25-dihydroxyvitamin D3 determined with a highly sensitive and precise LC-MS/MS method.
Collapse
Affiliation(s)
- Niek F Dirks
- Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, Amsterdam, The Netherlands
| | - Frans Martens
- Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, Amsterdam, The Netherlands
| | - Dirk Vanderschueren
- Department of Clinical and Experimental Medicine KU Leuven, Laboratory of Clinical and Experimental Endocrinology, Leuven, Belgium; Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Jaak Billen
- Department of Clinical and Experimental Medicine KU Leuven, Laboratory of Clinical and Experimental Endocrinology, Leuven, Belgium; Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Steven Pauwels
- Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
| | - Mariëtte T Ackermans
- Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, Amsterdam, The Netherlands
| | - Erik Endert
- Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, Amsterdam, The Netherlands
| | - Martin den Heijer
- Department of Internal Medicine, Endocrinology, VU University Medical Center, Amsterdam, The Netherlands
| | - Marinus A Blankenstein
- Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, Amsterdam, The Netherlands
| | - Annemieke C Heijboer
- Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, Amsterdam, The Netherlands.
| |
Collapse
|
|
23
|
Meems LMG, Mahmud H, Buikema H, Tost J, Michel S, Takens J, Verkaik-Schakel RN, Vreeswijk-Baudoin I, Mateo-Leach IV, van der Harst P, Plösch T, de Boer RA. Parental vitamin D deficiency during pregnancy is associated with increased blood pressure in offspring via Panx1 hypermethylation. Am J Physiol Heart Circ Physiol 2016; 311:H1459-H1469. [PMID: 27769995 DOI: 10.1152/ajpheart.00141.2016] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Revised: 10/05/2016] [Accepted: 10/10/2016] [Indexed: 11/22/2022]
Abstract
Vitamin D deficiency is one of the most common nutritional deficiencies worldwide. Maternal vitamin D deficiency is associated with increased susceptibility to hypertension in offspring, but the reasons for this remain unknown. The aim of this study was to determine if parental vitamin D deficiency leads to altered DNA methylation in offspring that may relate to hypertension. Male and female Sprague-Dawley rats were fed a standard or vitamin D-depleted diet. After 10 wk, nonsibling rats were mated. The conceived pups received standard chow. We observed an increased systolic and diastolic blood pressure in the offspring from depleted parents (F1-depl). Genome-wide methylation analyses in offspring identified hypermethylation of the promoter region of the Pannexin-1 (Panx1) gene in F1-depl rats. Panx1 encodes a hemichannel known to be involved in endothelial-dependent relaxation, and we demonstrated that in F1-depl rats the increase in blood pressure was associated with impaired endothelial relaxation of the large vessels, suggesting an underlying biological mechanism of increased blood pressure in children from parents with vitamin deficiency. Parental vitamin D deficiency is associated with epigenetic changes and increased blood pressure levels in offspring.
Collapse
Affiliation(s)
- Laura M G Meems
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Hasan Mahmud
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Hendrik Buikema
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jörg Tost
- Centre National de Génotypage, CEA-Institute de Génomique, Laboratory for Epigenetics and Environment, Evry, France
| | - Sven Michel
- Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany; and
| | - Janny Takens
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Rikst N Verkaik-Schakel
- Obstetrics and Gynaecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Inge Vreeswijk-Baudoin
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Irene V Mateo-Leach
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Pim van der Harst
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Torsten Plösch
- Obstetrics and Gynaecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Rudolf A de Boer
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;
| |
Collapse
|
|
24
|
Alsancak Y, Cengel A, Akyel A, Ozkan S, Sezenoz B, Unlu S, Kiziltunc E, Akboga MK, Alsancak AD, Elbeg S, Sahinarslan A, Yalcın MR. Relationship between serum vitamin D levels and angiographic severity and extent of coronary artery disease. Eur J Clin Invest 2015; 45:940-8. [PMID: 26248116 DOI: 10.1111/eci.12490] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Accepted: 07/01/2015] [Indexed: 12/29/2022]
Abstract
BACKGROUND Vitamin D is known for its effect in calcium and bone homeostasis. There is an increasing evidence for health benefits accomplished by activated vitamin D that go beyond these classical functions. Previous studies have suggested that lower vitamin D levels are associated with increased cardiovascular disease risk. Therefore, we aimed to evaluate relationship between vitamin D levels and extent and severity of coronary artery disease. MATERIALS AND METHODS A total of 746 patients in whom coronary angiography was performed between August 2012 and July 2013 were enrolled in this study. Serum vitamin D levels were measured, and patients were grouped according to their serum vitamin D levels (vitamin D <20 ng/mL (n = 602) Group 1 versus >20 ng/dL (n = 144) Group 2). Gensini score system was used to evaluate the association between serum vitamin D levels and severity and extent of coronary artery disease. RESULTS There was no significant difference between the groups in terms of baseline characteristics and demographic characteristics. Mean serum vitamin D levels of all patient cohort was 15.54 ± 7.46 ng/mL. Group 1 and Group 2 had an average serum vitamin D levels of 12.6 ± 3.3 ng/mL and 27.5 ± 7.8 ng/mL, respectively. Gensini score for all cohort was 26.25 ± 34.32. Group 1 had an average Gensini score of 26.4 ± 35.7; on the other hand, Gensini score was 25.5 ± 27.5 in Group 2 (P = 0.097). CONCLUSIONS This study failed to demonstrate significant relationship between serum vitamin D levels and the severity and extent of coronary artery disease. Further studies with more participation and homogenous groups with comparable individual and environmental features are needed to evaluate the association of serum vitamin D levels and cardiovascular diseases.
Collapse
Affiliation(s)
- Yakup Alsancak
- Department of Cardiology, Ataturk Education and Research Hospital, Ankara, Türkiye
| | - Atiye Cengel
- Department of Cardiology, Gazi University Medical Faculty, Ankara, Türkiye
| | - Ahmet Akyel
- Department of Cardiology, Dıskapı Education and Research Hospital, Ankara, Türkiye
| | - Selcuk Ozkan
- Department of Cardiology, 29 Mayıs State Hospital, Ankara, Türkiye
| | - Burak Sezenoz
- Department of Cardiology, Gazi Mustafa Kemal State Hospital, Ankara, Türkiye
| | - Serkan Unlu
- Department of Cardiology, Gazi University Medical Faculty, Ankara, Türkiye
| | - Emrullah Kiziltunc
- Department of Cardiology, Numune Education and Research Hospital, Ankara, Türkiye
| | - Mehmet Kadri Akboga
- Department of Cardiology, Turkiye Yuksek Ihtisas Education and Research Hospital, Ankara, Turkey
| | - Aybuke Demir Alsancak
- Department of Family Medicine, Numune Education and Research Hospital, Ankara, Türkiye
| | - Sehri Elbeg
- Department of Biochemistry, Gazi University Medical Faculty, Ankara, Türkiye
| | - Asife Sahinarslan
- Department of Cardiology, Gazi University Medical Faculty, Ankara, Türkiye
| | | |
Collapse
|
|
25
|
Links between Vitamin D Deficiency and Cardiovascular Diseases. BIOMED RESEARCH INTERNATIONAL 2015; 2015:109275. [PMID: 26000280 PMCID: PMC4427096 DOI: 10.1155/2015/109275] [Citation(s) in RCA: 155] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Accepted: 02/08/2015] [Indexed: 02/07/2023]
Abstract
The aim of the present paper was to review the most important mechanisms explaining the possible association of vitamin D deficiency and cardiovascular diseases, focusing on recent experimental and clinical data. Low vitamin D levels favor atherosclerosis enabling vascular inflammation, endothelial dysfunction, formation of foam cells, and proliferation of smooth muscle cells. The antihypertensive properties of vitamin D include suppression of the renin-angiotensin-aldosterone system, renoprotective effects, direct effects on endothelial cells and calcium metabolism, inhibition of growth of vascular smooth muscle cells, prevention of secondary hyperparathyroidism, and beneficial effects on cardiovascular risk factors. Vitamin D is also involved in glycemic control, lipid metabolism, insulin secretion, and sensitivity, explaining the association between vitamin D deficiency and metabolic syndrome. Vitamin D deficit was associated in some studies with the number of affected coronary arteries, postinfarction complications, inflammatory cytokines and cardiac remodeling in patients with myocardial infarction, direct electromechanical effects and inflammation in atrial fibrillation, and neuroprotective effects in stroke. In peripheral arterial disease, vitamin D status was related to the decline of the functional performance, severity, atherosclerosis and inflammatory markers, arterial stiffness, vascular calcifications, and arterial aging. Vitamin D supplementation should further consider additional factors, such as phosphates, parathormone, renin, and fibroblast growth factor 23 levels.
Collapse
|
|
26
|
Zhang W, Chen L, Zhang L, Xiao M, Ding J, Goltzman D, Miao D. Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central renin-angiotensin system in 1α(OH)ase knockout mice. Neurosci Lett 2015; 588:184-9. [PMID: 25576706 DOI: 10.1016/j.neulet.2015.01.013] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 12/31/2014] [Accepted: 01/05/2015] [Indexed: 12/21/2022]
Abstract
Previously, we reported that active vitamin D deficiency in mice causes secondary hypertension and cardiac dysfunction, but the underlying mechanism remains largely unknown. To clarify whether exogenous active vitamin D rescues hypertension by normalizing the altered central renin-angiotensin system (RAS) via an antioxidative stress mechanism, 1-alpha-hydroxylase [1α(OH)ase] knockout mice [1α(OH)ase(-/-)] and their wild-type littermates were fed a normal diet alone or with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a high-calcium, high-phosphorus "rescue" diet with or without antioxidant N-acetyl-l-cysteine (NAC) supplementation for 4 weeks. Compared with their wild-type littermates, 1α(OH)ase(-/-)mice had high mean arterial pressure, increased levels of renin, angiotensin II (Ang II), and Ang II type 1 receptor, and increased malondialdehyde levels, but decreased anti-peroxiredoxin I and IV proteins and the antioxidative genes glutathione reductase (Gsr) and glutathione peroxidase 4 (Gpx4) in the brain samples. Except Ang II type 1 receptor, these pathophysiological changes were rescued by exogenous 1,25(OH)2D3 or NAC plus rescue diet, but not by rescue diet alone. We conclude that 1,25(OH)2D3 normalizes the altered central RAS in 1α(OH)ase(-/-)mice, at least partially, through a central antioxidative mechanism.
Collapse
Affiliation(s)
- Wei Zhang
- Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu 210029, PR China; Department of Human Anatomy, Kangda College, Lianyungang, PR China
| | - Lulu Chen
- Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu 210029, PR China
| | - Luqing Zhang
- Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu 210029, PR China.
| | - Ming Xiao
- Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu 210029, PR China
| | - Jiong Ding
- Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu 210029, PR China
| | - David Goltzman
- Calcium Research Laboratory, McGill University Health Center and Department of Medicine, McGill University, Montréal, Québec, Canada
| | - Dengshun Miao
- Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu 210029, PR China
| |
Collapse
|
|
27
|
Martínez-Miguel P, Valdivielso JM, Medrano-Andrés D, Román-García P, Cano-Peñalver JL, Rodríguez-Puyol M, Rodríguez-Puyol D, López-Ongil S. The active form of vitamin D, calcitriol, induces a complex dual upregulation of endothelin and nitric oxide in cultured endothelial cells. Am J Physiol Endocrinol Metab 2014; 307:E1085-96. [PMID: 25336523 DOI: 10.1152/ajpendo.00156.2014] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Despite the presence of vitamin D receptor (VDR) in endothelial cells, the effect of vitamin D on endothelial function is unknown. An unbalanced production of vasoactive endothelial factors such as nitric oxide (NO) or endothelin-1 (ET-1) results in endothelial dysfunction, which can alter the normal cardiovascular function. Present experiments were devoted to assess the effect of active vitamin D (calcitriol) on the synthesis of endothelial vasoactive factors. The results were that, in cells, calcitriol increased ET-1 and NO productions, which were measured by ELISA and fluorimetric assay, respectively. Calcitriol also increased endothelin-converting enzyme-1 (ECE-1) and endothelial-nitric oxide synthase (eNOS) activities, their mRNA (qPCR), their protein expressions (Western-blot), and their promoter activities (transfection assays). Calcitriol did not change prepro-ET-1 mRNA. The effect was specific to VDR activation because when VDR was silenced by siRNA, the observed effects disappeared. Mechanisms involved in each upregulation differed. ECE-1 upregulation depended on AP-1 activation, whereas eNOS upregulation depended directly on VDR activation. To evaluate the in vivo consequences of acute calcitriol treatment, normal Wistar rats were treated with a single ip injection of 400 ng/kg calcitriol and euthanized 24 h later. Results confirmed those observed in cells, that production and expression of both factors were increased by calcitriol. Besides, calcitriol-treated rats showed a slight rise in mean blood pressure, which decreased when pretreated with FR-901533, an ECE-1 antagonist. We conclude that calcitriol increases the synthesis of both ET-1 and NO in endothelial cells. However, the ET-1 upregulation seems to be biologically more relevant, as animals acutely treated with calcitriol show slight increases in blood pressure.
Collapse
Affiliation(s)
- Patricia Martínez-Miguel
- Research Unit and Nephrology Section, Fundación para la Investigación Biomédica del Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
| | | | | | - Pablo Román-García
- Servicio de Metabolismo Mineral y Óseo, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Spain; Instituto Reina Sofía de Investigación Nefrológica, Madrid, Spain; and
| | | | - Manuel Rodríguez-Puyol
- Instituto Reina Sofía de Investigación Nefrológica, Madrid, Spain; and Physiology Department, Universidad de Alcalá, Madrid, Spain
| | - Diego Rodríguez-Puyol
- Research Unit and Nephrology Section, Fundación para la Investigación Biomédica del Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain; Instituto Reina Sofía de Investigación Nefrológica, Madrid, Spain; and
| | - Susana López-Ongil
- Research Unit and Instituto Reina Sofía de Investigación Nefrológica, Madrid, Spain; and
| |
Collapse
|
|
28
|
Andrés V. Vitamin D puts the brakes on angiotensin II-induced oxidative stress and vascular smooth muscle cell senescence. Atherosclerosis 2014; 236:444-7. [PMID: 25173069 DOI: 10.1016/j.atherosclerosis.2014.07.031] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Accepted: 07/26/2014] [Indexed: 02/08/2023]
Abstract
Signaling via both vitamin D (VitD) and the renin-angiotensin system (RAS) plays important roles in physiological processes. Evidence has mounted linking cardiovascular disease to both increased activity of the RAS and VitD deficiency. Although several studies have established functional relationships between the RAS and VitD, many aspects of their complex interaction remain unknown. In this issue of Atherosclerosis, Valcheva and colleagues show that defective VitD signaling can promote vascular damage by inducing premature senescence of smooth muscle cells due to elevated local production of angiotensin II and reactive oxygen species, and upregulation of the tumor suppressor p57(Kip2).
Collapse
Affiliation(s)
- Vicente Andrés
- Laboratory of Molecular and Genetic Cardiovascular Pathophysiology, Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
| |
Collapse
|
|
29
|
Sahin I, Okuyan E, Gungor B, Kaya A, Avci II, Biter Hİ, Cetin S, Enhos A, Avsar M, Dinçkal MH. Lower vitamin D level is associated with poor coronary collateral circulation. SCAND CARDIOVASC J 2014; 48:278-83. [PMID: 24978423 DOI: 10.3109/14017431.2014.940062] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVES Vitamin D regulates calcium and bone homeostasis, and parathyroid hormone (PTH) secretion. Cross-sectional associations between lower vitamin D levels and cardiovascular diseases have been reported, but the relationship between vitamin D levels and collateral arteries in stable coronary artery disease (CAD) has not been reported before. DESIGN Two hundred and fourteen patients with above 95% stenosis in at least one epicardial coronary artery were consecutively recruited after coronary angiography (CAG) during the winter season. The coronary collateral circulation (CCC) was graded using Rentrop classification. Poor CCC group included patients with Rentrop Grade 0-1 CCC and control group included patients with Rentrop Grade 2-3 CCC. Vitamin D and PTH levels were measured on the day of CAG. RESULTS In the poor CCC group, vitamin D levels were lower (34 ± 25 pmol/L vs. 49 ± 33 pmol/L; p = 0.01) and the prevalence of vitamin D deficiency (< 37 pmol/L) was higher (67% vs. 43%; p = 0.01) compared to the controls. PTH levels, calcium, and phosphate levels were not significantly different between the groups. Female gender, lower HDL cholesterol, and lower vitamin D levels were independently correlated with poor CCC in the study population. CONCLUSION Lower vitamin D levels may be associated with poor collateral development in patients with stable CAD.
Collapse
Affiliation(s)
- Irfan Sahin
- Department of Cardiology, Bagcilar Training and Research Hospital , Istanbul , Turkey
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Sulistyoningrum DC, Gasevic D, Green TJ, Lear SA, Devlin AM. Adiposity and the relationship between vitamin D and blood pressure. Metabolism 2013; 62:1795-802. [PMID: 23987237 DOI: 10.1016/j.metabol.2013.07.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Revised: 07/06/2013] [Accepted: 07/17/2013] [Indexed: 01/28/2023]
Abstract
OBJECTIVE Circulating vitamin D (25OHD) concentrations are negatively associated with blood pressure (BP) but little is known about the mechanisms for this relationship. Adiposity is positively associated with BP and inversely with circulating 25OHD concentrations but no studies have assessed the relationship between plasma 25OHD and adiposity on BP. The goal of this study is to investigate if the association between plasma 25OHD and BP is mediated by adiposity. MATERIALS/METHODS The relationship between plasma 25OHD, systolic and diastolic BP, and adiposity [BMI, waist circumference, visceral adipose tissue (VAT)] was assessed in a multi-ethnic cross-sectional study of Aboriginal (n=151), Chinese (n=190), European (n=170), and South Asian (n=176) participants by linear regression models. RESULTS Plasma 25OHD concentrations were negatively associated with systolic (standardized B=-0.191, P<0.001) and diastolic BP (standardized B=-0.196, P<0.001) in models adjusted for age, sex, ethnicity, family history of CVD, smoking status, alcohol consumption, and physical activity. The negative relationship between plasma 25OHD concentrations and systolic and diastolic BP was attenuated after the addition of BMI, waist circumference, and VAT to the models, but the relationship remained significant. Plasma 25OHD concentrations accounted for 0.7% and 0.8% of the variance in systolic and diastolic BP, respectively. CONCLUSION These findings suggest that the relationship between vitamin D and BP is independent of adiposity. Further studies are required to determine the mechanisms by which vitamin D affects BP.
Collapse
Affiliation(s)
- Dian C Sulistyoningrum
- Department of Pathology and Laboratory Medicine, University of British Columbia, Child and Family Research Institute, Vancouver, Canada
| | | | | | | | | |
Collapse
|
|
31
|
Association of vitamin D status and blood pressure response after renal denervation. Clin Res Cardiol 2013; 103:41-7. [PMID: 24173883 DOI: 10.1007/s00392-013-0621-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Accepted: 09/17/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND Vitamin D deficiency is associated with hypertension; however, it is unclear whether vitamin D influences therapeutic blood pressure reduction. Renal sympathetic denervation (RDN) reduces blood pressure in resistant hypertension. We hypothesized that vitamin D might influence blood pressure response to RDN. METHODS Vitamin D was measured in 101 patients with resistant hypertension undergoing RDN. The associations between vitamin D status and systolic blood pressure (SBP) reduction 6 months after RDN were analyzed. RESULTS Mean office SBP at baseline was 171.5 ± 2 mmHg. After RDN, mean office SBP was reduced by 28.4 ± 2.3 mmHg (p = 0.007). 85 patients (84.2 %) had SBP reductions >10 mmHg (responders). Vitamin D concentrations were lower in non-responders as compared to responders (9.9 ± 4.5 vs. 13.7 ± 7.4 ng/ml, p = 0.008). Non-responders (n = 16, 15.8 %), more often had a vitamin D concentration below the median as compared to responders (81 vs. 46 %, p = 0.013). The percentage of patients with normal vitamin D concentrations increased with increasing tertiles of SBP reduction (p for trend = 0.020). In patients with vitamin D concentrations below the median, SBP reduction was lower as compared to patients with a vitamin D concentration above the median (23.5 ± 3.2 vs. 33.7 ± 3.2 mmHg, p = 0.026). Baseline vitamin D concentrations correlated with SBP reduction (r = 0.202, p = 0.043). CONCLUSIONS In patients with resistant hypertension, low vitamin D concentrations were associated with a decreased SBP response and a higher rate of non-response.
Collapse
|
|
32
|
Ku YC, Liu ME, Ku CS, Liu TY, Lin SL. Relationship between vitamin D deficiency and cardiovascular disease. World J Cardiol 2013; 5:337-346. [PMID: 24109497 PMCID: PMC3783986 DOI: 10.4330/wjc.v5.i9.337] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Accepted: 09/04/2013] [Indexed: 02/06/2023] Open
Abstract
Epidemiological studies have found that low 25-hydroxyvitamin D levels may be associated with coronary risk factors and adverse cardiovascular outcomes. Additionally, vitamin D deficiency causes an increase in parathyroid hormone, which increases insulin resistance and is associated with diabetes, hypertension, inflammation, and increased cardiovascular risk. In this review, we analyze the association between vitamin D supplementation and the reduction in cardiovascular disease. The role of vitamin D deficiency in cardiovascular morbidity and mortality is still controversial, and larger scale, randomized placebo controlled trials are needed to investigate whether oral vitamin D supplementation can reduce cardiovascular risk. Given the low cost, safety, and demonstrated benefit of higher 25-hydroxyvitamin D levels, vitamin D supplementation should become a public health priority for combating common and costly chronic cardiovascular diseases.
Collapse
|
|
33
|
Zubair M, Malik A, Meerza D, Ahmad J. 25-Hydroxyvitamin D [25(OH)D] levels and diabetic foot ulcer: is there any relationship? Diabetes Metab Syndr 2013; 7:148-153. [PMID: 23953180 DOI: 10.1016/j.dsx.2013.06.008] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIMS In recent years, there has been an effort to understand possible roles of 25(OH)D, including its role in the immune system particularly on T cell medicated immunity, pancreatic insulin secretion and insulin action. 25(OH)D stimulates the cell differentiation and reduces cell proliferation, which is essential for cell growth and wound healing. However, data on the association between low level of plasma 25(OH)D and diabetic foot syndrome are scarce. MATERIALS AND METHODS Circulating plasma levels of 25(OH)D were measured in diabetic patients with ulcer (n=162) and without ulcer (n=162) in a prospective cohort hospital based study. RESULTS Of these patients, 85.1% had type 2 diabetes. Subjects with diabetic foot ulcer showed lower median plasma level of 25(OH)D [6.3(4.2-11.1) vs 28.0(21.4-37.0)] ng/ml after adjusting the age and BMI. Regardless of the low levels of 25(OH)D in cases and controls, it was associated with neuropathy, sex (female), duration of ulcer healing, and smoking status and independent of confounding factors, including BMI (kg/m²), A1c (%), hypertension, nephropathy, foot ulcer, retinopathy, CAD, PAD, HDL-C (mg/dl) and LDL-C (mg/dl). The factors which predict the risk of developing ulcer independent of 25(OH)D status were A1c (>6.9%) [OR 4.37; RR 1.77], HDL-C (<40mg/dl) [OR 1.16; RR 1.07], LDL-C (>100mg/dl) [OR 1.07; RR 1.03], triglycerides (>200mg/dl) [OR 1.40; RR 1.19], neuropathy [OR 6.88; RR 3.12], retinopathy [OR 3.34; RR 1.91], hypertension [OR 1.64; RR 1.28], nephropathy [OR 3.12; RR 1.87] and smoking [OR 4.53; RR 2.99] using odds and risk ratios. CONCLUSION It is not clear whether the suppression of delayed wound healing seen during 25(OH)D deficiency is due to the secondary effect or is a direct action of vitamin D on certain components of the immune system. Long-term randomized trials are needed to see the impact of vitamin D supplementation on the outcome of diabetic foot patients.
Collapse
Affiliation(s)
- Mohammad Zubair
- Department of Microbiology, Faculty of Medicine, J.N. Medical College, Aligarh Muslim University, Aligarh 202002, India.
| | | | | | | |
Collapse
|
|
34
|
Liu NQ, Ouyang Y, Bulut Y, Lagishetty V, Chan SY, Hollis BW, Wagner C, Equils O, Hewison M. Dietary vitamin D restriction in pregnant female mice is associated with maternal hypertension and altered placental and fetal development. Endocrinology 2013; 154:2270-80. [PMID: 23677931 DOI: 10.1210/en.2012-2270] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Epidemiology has linked vitamin D deficiency with preeclampsia in humans. We hypothesized that low vitamin D status in pregnant mice may lead to symptoms of preeclampsia. Female BL6 mice were raised on vitamin D-sufficient or -deficient diets from weeks 4 of age and then mated with vitamin D-sufficient BL6 males at week 8. The resulting pregnant mice were either allowed to deliver pups and monitored for blood pressure (BP) and weight of offspring or euthanized at day 14 or 18 of gestation (E14 or E18) for analysis of serum, placental/kidney tissues, and fetuses. At E14 serum concentrations of 25-hydroxyvitamin D (30.1 ± 5.0 vs 1.8 ± 0.6 ng/mL, P < .001) and 1,25-dihydroxyvitamin D (119.5 ± 18.7 vs 37.4 ± 5.1 pg/mL, P < .01) were higher in sufficient vs deficient pregnant mice. At E14 BP was significantly elevated in vitamin D-deficient pregnant mice relative to vitamin D-sufficient mice for both systolic BP (124.89 ± 2.28 vs 105.34 ± 3.61 mm Hg, P < .001) and mean arterial pressure (115.33 ± 1.93 vs 89.33 ± 5.02 mm Hg, P < .001). This elevation continued through pregnancy until 7 days postpartum (PP7) but returned to baseline by PP14. Analysis of maternal kidneys showed increased expression of mRNA for renin and the angiotensin II receptor (3- and 4-fold, respectively) in vitamin D-deficient vs -sufficient mice at E14. Histological analysis of E14 placentas from vitamin D-deficient mice showed decreased vascular diameter within the labyrinth region. E14 and E18 fetuses from vitamin D-deficient mice were larger than those from vitamin D-sufficient mothers. However, by PP14 pups from vitamin D-deficient mothers weighed significantly less than those from vitamin D-sufficient mothers. Resupplementation of vitamin D periconceptually partially reversed the effects of vitamin D deficiency. These data provide further evidence that low vitamin D status may predispose pregnant women to dysregulated placental development and elevated blood pressure.
Collapse
Affiliation(s)
- Nancy Q Liu
- Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | | | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Helvacı A, Copur B, Adaş M. Correlation between Left Ventricular Mass Index and Calcium Metabolism in Patients with Essential Hypertension. Balkan Med J 2013; 30:85-9. [PMID: 25207075 DOI: 10.5152/balkanmedj.2012.097] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2012] [Accepted: 10/01/2012] [Indexed: 01/19/2023] Open
Abstract
OBJECTIVE To determine the correlation between left ventricular mass index and calcium metabolism in patients with essential hypertension. STUDY DESIGN Cross sectional case-control study. MATERIAL AND METHODS Twenty-seven patients with essential hypertension and 20 healthy individuals were compared with respect to calciotropic hormones, left ventricular mass index (LVMI), and urinary and serum biochemical parameters. The correlations between parathormone, vitamin D, and calcitonin levels and LVMI and blood pressure elevation were determined. RESULTS The parathormone level was significantly higher (p=0.006) and vitamin D level was significantly lower (p=0.01) in the patient group compared with the control group. However, the two groups were similar in terms of albumin-corrected calcium levels, which were within the normal range (p=0.988). The serum sodium (p=0.014) and urinary calcium (p=0.003) levels and LVMI (p<0.01) were also significantly higher in the patient group. No significant correlations were determined between ambulatory blood pressure and parathormone and vitamin D levels, but a significant correlation was found between LVMI and parathormone level (p=0.06) in hypertensive patients. CONCLUSION Essential hypertension alters calcium metabolism, causing calciuresis by hypernatremia. Parathormone release increases to compensate for this, and leads to protein synthesis, which in turn provokes the development of myocardial hypertrophy.
Collapse
Affiliation(s)
- Ayşen Helvacı
- Clinic of 2 Internal Medicine, Okmeydanı Training and Research Hospital, İstanbul, Turkey
| | - Besime Copur
- Clinic of 2 Internal Medicine, Okmeydanı Training and Research Hospital, İstanbul, Turkey
| | - Mine Adaş
- Clinic of 2 Internal Medicine, Okmeydanı Training and Research Hospital, İstanbul, Turkey
| |
Collapse
|
|
36
|
|
|
37
|
Ferder M, Inserra F, Manucha W, Ferder L. The world pandemic of vitamin D deficiency could possibly be explained by cellular inflammatory response activity induced by the renin-angiotensin system. Am J Physiol Cell Physiol 2013; 304:C1027-39. [PMID: 23364265 DOI: 10.1152/ajpcell.00403.2011] [Citation(s) in RCA: 100] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This review attempts to show that there may be a relationship between inflammatory processes induced by chronic overstimulation of the renin-angiotensin system (RAS) and the worldwide deficiency of vitamin D (VitD) and that both disorders are probably associated with environmental factors. Low VitD levels represent a risk factor for several apparently different diseases, such as infectious, autoimmune, neurodegenerative, and cardiovascular diseases, as well as diabetes, osteoporosis, and cancer. Moreover, VitD insufficiency seems to predispose to hypertension, metabolic syndrome, left ventricular hypertrophy, heart failure, and chronic vascular inflammation. On the other hand, inappropriate stimulation of the RAS has also been associated with the pathogenesis of hypertension, heart attack, stroke, and hypertrophy of the left ventricle and vascular smooth muscle cells. Because VitD receptors (VDRs) and RAS receptors are almost distributed in the same tissues, a possible link between VitD and the RAS is even more plausible. Furthermore, from an evolutionary point of view, both systems were developed simultaneously, actively participating in the regulation of inflammatory and immunological mechanisms. Changes in RAS activity and activation of the VDR seem to be inversely related; thus any changes in one of these systems would have a completely opposite effect on the other, making it possible to speculate that the two systems could have a feedback relationship. In fact, the pandemic of VitD deficiency could be the other face of increased RAS activity, which probably causes lower activity or lower levels of VitD. Finally, from a therapeutic point of view, the combination of RAS blockade and VDR stimulation appears to be more effective than either RAS blockade or VDR stimulation individually.
Collapse
Affiliation(s)
- Marcelo Ferder
- Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
| | | | | | | |
Collapse
|
|
38
|
Ess M, Heitmair-Wietzorrek K, Frick M, Umlauf N, Ulmer H, Poelzl G. Serum Phosphate and Long-Term Outcome Among Patients With Stable Heart Failure. J Card Fail 2013; 19:25-30. [DOI: 10.1016/j.cardfail.2012.11.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2012] [Revised: 11/01/2012] [Accepted: 11/14/2012] [Indexed: 01/09/2023]
|
|
39
|
Omega-3 Fatty acids and vitamin d in cardiology. Cardiol Res Pract 2012; 2012:729670. [PMID: 23346457 PMCID: PMC3549392 DOI: 10.1155/2012/729670] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2012] [Revised: 08/15/2012] [Accepted: 09/07/2012] [Indexed: 12/24/2022] Open
Abstract
Dietary modification and supplementation play an increasingly important role in the conservative treatment of cardiovascular disease. Current interest has focused on n-3 polyunsaturated fatty acids (PUFA) and vitamin D. Clinical trial results on this subject are contradictory in many aspects. Several studies indicate that n-3 PUFA consumption improves vascular and cardiac hemodynamics, triglycerides, and possibly endothelial function, autonomic control, inflammation, thrombosis, and arrhythmia. Experimental studies show effects on membrane structure and associated functions, ion channel properties, genetic regulation, and production of anti-inflammatory mediators. Clinical trials evaluating a possible reduction in cardiovascular disease by n-3 PUFA have shown different results. Supplementation of vitamin D is common regarding prevention and treatment of osteoporosis. But vitamin D also seems to have several effects on the cardiovascular system. Vitamin D deficiency appears to be related to an increase in parathyroid hormone levels and can predispose to essential hypertension and left ventricular hypertrophy, increased insulin resistance, and eventually to atherosclerosis and adverse cardiovascular events. Randomized prospective clinical trials are needed to determine whether vitamin D and omega-3 FA supplementation therapy should be recommended as a routine therapy for primary or secondary prevention of cardiovascular disease.
Collapse
|
|
40
|
Abstract
The prevalence of both hypertension and vitamin D deficiency is high. The discovery of the vitamin D receptor and its possible effects on components of the cardiovascular system influencing blood pressure, such as the renin angiotensin system, the heart, the kidney and the blood vessels, has generated the hope that vitamin D therapy could be a new target for the treatment for hypertensive patients. Cross-sectional studies have clearly shown an association between low levels of vitamin D and hypertension. This association is not as clear in longitudinal studies. Finally, evidence from randomized controlled trials specifically designed to test the hypothesis of a blood pressure lowering effect of vitamin D is weak. Therefore, there is actually not enough evidence to recommend giving vitamin D to reduce blood pressure in hypertensive patients.
Collapse
Affiliation(s)
- Gregoire Wuerzner
- Service of nephrology and hypertension, Lausanne University Hospital, Lausanne, Switzerland
| | | | | |
Collapse
|
|
41
|
Takács I, Benkő I, Toldy E, Wikonkál N, Szekeres L, Bodolay E, Kiss E, Jambrik Z, Szabó B, Merkely B, Valkusz Z, Kovács T, Szabó A, Grigoreff O, Nagy Z, Demeter J, Horváth HC, Bittner N, Várbíró S, Lakatos P. [Hungarian consensus regarding the role of vitamin D in the prevention and treatment of diseases]. Orv Hetil 2012; 153 Suppl:5-26. [PMID: 22934332 DOI: 10.1556/oh.2012.29410] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The metabolism of vitamin D is unique in the human body and its diverse effects are present in almost every organ. Vitamin D deficiency is one of the most prominent health issues in the civilized world. For the solution of this concern an extensive collaboration is imperative. Recognizing this necessity the most prominent Hungarian medical associations fighting with the effects of vitamin D deficiency worked out a collective consensus on the importance, diagnosis, prevention and suggested therapy of vitamin D deficiency. Along with the clinical guidelines of the different associations, the result of this consensus could serve as guidance for the practicing doctors in the prevention and therapy of vitamin D deficiency. In addition the consensus aims to direct the attention of decision-makers and the general public on the significance of this issue.
Collapse
Affiliation(s)
- István Takács
- Altalános Orvostudományi Kar, I. Belgyógyászati Klinika, Budapest
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Heshmat R, Tabatabaei-Malazy O, Abbaszadeh-Ahranjani S, Shahbazi S, Khooshehchin G, Bandarian F, Larijani B. Effect of vitamin D on insulin resistance and anthropometric parameters in Type 2 diabetes; a randomized double-blind clinical trial. Daru 2012; 20:10. [PMID: 23351271 PMCID: PMC3555787 DOI: 10.1186/2008-2231-20-10] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Accepted: 07/10/2012] [Indexed: 12/11/2022] Open
Abstract
UNLABELLED BACKGROUND & THE PURPOSE OF THE STUDY: Prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. To reduce its risk and progression, preventive strategies are needed. Vitamin supplementation such as vitamin D is one of the strategies. This study was designed to investigate the effect of injection of vitamin D on insulin resistance and anthropometric parameters in T2DM. METHODS This randomized double-blind clinical trial was conducted with 42 diabetic patients in two groups; intervention group with single intramuscular injection of 300,000 International Unit (IU) of vitamin D3 and the placebo group. After recording demographic and anthropometric factors (waist circumference, blood pressure and body mass index), fasting blood samples was taken for measurement of blood glucose, 25-hydroxyvitamin D3 (25-OHD3), insulin, glycosylated hemoglobin A1c (HbA1c) and estimation of Homeostasis Model Assessment Index (HOMA) in two times; before study and after three months. RESULTS Two groups had similar baseline characteristics (each group = 21 subjects). Three months after vitamin D injection, HbA1c, anthropometric factors and HOMA index in intervention group stayed constant, however, serum 25- OHD3 was significantly increased (p = 0.007). CONCLUSION The present data is not convincing and further studies with large sample sizes are needed to show the definite effect of injection of vitamin D on control of diabetes and its risk.
Collapse
Affiliation(s)
- Ramin Heshmat
- Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, 5th floor, Dr. Shariati Hospital, North Kargar Ave, 14114 Tehran, Iran
| | - Ozra Tabatabaei-Malazy
- Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, 5th floor, Dr. Shariati Hospital, North Kargar Ave, 14114 Tehran, Iran
| | - Shabnam Abbaszadeh-Ahranjani
- Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, 5th floor, Dr. Shariati Hospital, North Kargar Ave, 14114 Tehran, Iran
| | - Samimeh Shahbazi
- Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, 5th floor, Dr. Shariati Hospital, North Kargar Ave, 14114 Tehran, Iran
| | - Ghazal Khooshehchin
- Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, 5th floor, Dr. Shariati Hospital, North Kargar Ave, 14114 Tehran, Iran
| | - Fathemeh Bandarian
- Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, 5th floor, Dr. Shariati Hospital, North Kargar Ave, 14114 Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, 5th floor, Dr. Shariati Hospital, North Kargar Ave, 14114 Tehran, Iran
| |
Collapse
|
|
43
|
Payne JF, Ray R, Watson DG, Delille C, Rimler E, Cleveland J, Lynn MJ, Tangpricha V, Srivastava SK. Vitamin D insufficiency in diabetic retinopathy. Endocr Pract 2012; 18:185-93. [PMID: 21940279 DOI: 10.4158/ep11147.or] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
OBJECTIVE To assess the relationship between vitamin D status and diabetic retinopathy. METHODS A clinic-based, cross-sectional study was conducted at Emory University, Atlanta, Georgia. Overall, 221 patients were classified into 5 groups based on diabetes status and retinopathy findings: no diabetes or ocular disease (n = 47), no diabetes with ocular disease (n = 51), diabetes with no background diabetic retinopathy (n = 41), nonproliferative diabetic retinopathy (n = 40), and proliferative diabetic retinopathy (PDR) (n = 42). Patients with type 1 diabetes and those taking >1,000 IU of vitamin D daily were excluded from the analyses. Study subjects underwent dilated funduscopic examination and were tested for hemoglobin A1c, serum creatinine, and 25-hydroxyvitamin D [25(OH)D] levels between December 2009 and March 2010. RESULTS Among the study groups, there was no statistically significant difference in age, race, sex, or multivitamin use. Patients with diabetes had lower 25(OH)D levels than did those without diabetes (22.9 ng/mL versus 30.3 ng/mL, respectively; P<.001). The mean 25(OH)D levels, stratified by group, were as follows: no diabetes or ocular disease = 31.9 ng/mL; no diabetes with ocular disease = 28.8 ng/mL; no background diabetic retinopathy = 24.3 ng/mL; nonproliferative diabetic retinopathy = 23.6 ng/mL; and PDR = 21.1 ng/mL. Univariate analysis of the 25(OH)D levels demonstrated statistically significant differences on the basis of study groups, race, body mass index, multivitamin use, hemoglobin A1c, serum creatinine level, and estimated glomerular filtration rate. In a multivariate linear regression model with all potential confounders, only multivitamin use remained significant (P<.001). CONCLUSION This study suggests that patients with diabetes, especially those with PDR, have lower 25(OH)D levels than those without diabetes.
Collapse
Affiliation(s)
- John F Payne
- Department of Vitreoretinal Surgery and Disease, Emory University, Atlanta, Georgia 30322, USA.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Alemzadeh R, Kichler J. Parathyroid hormone is associated with biomarkers of insulin resistance and inflammation, independent of vitamin D status, in obese adolescents. Metab Syndr Relat Disord 2012; 10:422-9. [PMID: 22849753 DOI: 10.1089/met.2012.0056] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND 25-Hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) have been shown to correlate with several markers of metabolic syndrome in adult populations. We evaluated the relationship between circulating intact parathyroid hormone (iPTH) and 25(OH)D and indices of metabolic syndrome in obese adolescents. METHODS Body mass index (BMI), body composition, 25(OH)D, iPTH, fasting lipids, glucose, high-sensitivity C-reactive protein (hsCRP), glycosylated hemoglobin (HbA1c), insulin, and the homeostatic model assessment for insulin resistance (HOMA-IR) were evaluated in 133 obese adolescents. RESULTS Vitamin D deficiency [25(OH)D <50 nmol/L] was present in 45.1% of all patients, with higher prevalence in African-American (AA) and Hispanic (H) than Caucasian (C) subgroups (63.9% and 56.4% vs. 25.9%; P<0.001). iPTH and 25(OH)D were inversely correlated (r=-0.75; P<0.0001), with AA displaying a higher iPTH: 25(OH)D ratio than H and C subgroups (P<0.05). Whereas fat mass (FM) was negatively correlated with 25(OH)D (r=-0.30; p<0.001), it was positively correlated with iPTH levels (r=0.38; P<0.0001). Metabolic syndrome was identified in 57.9% of the cohort with higher iPTH, iPTH:25(OH)D ratio, but lower 25(OH)D than participants without metabolic syndrome (P<0.02). Whereas iPTH showed main effects for hsCRP (β=0.24, t=2.61, P<0.05) and triglycerides:high-density lipoprotein cholesterol (TG:HDL-C) (β=0.21, t=2.13, p<0.05), independent of serum 25(OH)D, it did not reveal a main effect for HOMA-IR. CONCLUSIONS Metabolic syndrome is associated with a higher iPTH:25(OH)D ratio than those without metabolic syndrome, implying greater risk of cardiovascular morbidities among AA subjects than other ethnic groups. Furthermore, the serum iPTH level is a predictor of chronic inflammation and dyslipidemia, independent of 25(OH)D.
Collapse
Affiliation(s)
- Ramin Alemzadeh
- Department of Pediatrics, University of Illinois at Chicago, Chicago, IL 60612, USA.
| | | |
Collapse
|
|
45
|
Kim H, Kang SW, Yoo TH, Kim MS, Kim SI, Kim YS, Choi KH. The impact of pretransplant 25-hydroxy vitamin D deficiency on subsequent graft function: an observational study. BMC Nephrol 2012; 13:22. [PMID: 22533967 PMCID: PMC3393620 DOI: 10.1186/1471-2369-13-22] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2011] [Accepted: 04/25/2012] [Indexed: 01/20/2023] Open
Abstract
Background In addition to its canonical role in musculoskeletal health, several reports have demonstrated that serum vitamin D level may influence kidney function. However, the effect of pretransplant serum vitamin D level on subsequent graft function has not been explored. Therefore, this study was undertaken to examine the effect of serum vitamin D level at the time of kidney transplantation (KT) on subsequent graft function. Methods We analyzed 106 patients who underwent KT and for whom 25-hydroxy vitamin D (25-OHD) levels were measured during hospitalization prior to transplantation. We measured estimated glomerular filtration rates (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula at baseline and at six-month intervals up to 36 months after KT. Results 38.7% of the patients were diagnosed with 25-OHD deficiency defined as less than 10 ng/mL. Recipient gender (female vs. male, odds ratio [OR] 3.30, 95% CI 1.33-8.21, P = 0.010), serum albumin level (per 1 mg/dl increase, OR 0.35, 95% CI 0.13-0.98, P = 0.047), and predominant renal replacement therapy modality before KT (P < 0.001) were found to be independent pretransplant risk factors for 25-OHD deficiency by multivariate logistic regression analysis. Subsequent repeated measures analysis of covariance revealed that 25-OHD level had the only significant main effect on eGFR during the 36-month follow-up period [F (1, 88) = 12.07, P = 0.001]. Conclusions Pretransplant 25-OHD deficiency was significantly associated with a lower post-transplant eGFR, suggesting that 25-OHD may play an important role in maintaining graft function after KT.
Collapse
Affiliation(s)
- Hyunwook Kim
- Department of Internal Medicine, Wonkwang University College of Medicine, Sanbon Hospital, Kyunggi-do, Korea
| | | | | | | | | | | | | |
Collapse
|
|
46
|
Peterlik M. Vitamin D insufficiency and chronic diseases: hype and reality. Food Funct 2012; 3:784-94. [PMID: 22695493 DOI: 10.1039/c2fo10262e] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
In recent years an increasing number of observational studies have suggested that a low vitamin D status contributes to the development of all sorts of chronic diseases. In reality, however, studies that had been adequately controlled for confounding factors ruled out any link between vitamin D insufficiency and, for example, metabolic disorders, arterial hypertension, multiple sclerosis or cognitive dysfunction. Furthermore, a role of vitamin D insufficiency in autoimmune diseases is evident only in animal models but has not yet been established in humans. In respect to many malignancies, vitamin D insufficiency is only one out of many risk factors and its specific impact on disease incidence has never been assessed. There is convincing evidence, however, that vitamin D insufficiency is a major risk factor for osteoporosis, colorectal and breast cancer as well as for cardiovascular disease and mortality. However, it is debatable that circulating 25-hydroxyvitamin D concentrations of 100-150 nmol l(-1) are required for optimal health outcomes. These are overestimates which would afford to raise vitamin D intake to 4000 IU day(-1). In reality, high doses of vitamin D can cause serious health problems because of the U-shaped dose-response relationships that exist in some cases. Data from large cohort studies clearly indicate that serum 25-(OH)D concentrations around 50 nmol l(-1) are sufficient to minimize the risk of osteoporotic fractures, colorectal and breast cancer, and cardiovascular mortality. The fact that the risk-reducing potential of vitamin D depends on adequate calcium nutrition is widely ignored. I here summarize the evidence that efficient disease prevention does not require intake of more vitamin D and calcium than currently recommended for maintaining optimal bone health.
Collapse
Affiliation(s)
- Meinrad Peterlik
- Medical University of Vienna, Department of Pathophysiology, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
| |
Collapse
|
|
47
|
Ish-Shalom M, Sack J, Vechoropoulos M, Shaish A, Entin-Meer M, Kamari Y, Maysel-Auslender S, Keren G, Harats D, Stern N, Tordjman K. Low-dose calcitriol decreases aortic renin, blood pressure, and atherosclerosis in apoe-null mice. J Atheroscler Thromb 2012; 19:422-34. [PMID: 22659526 DOI: 10.5551/jat.9621] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
AIMS To determine whether low-dose calcitriol attenuates atherosclerosis in apoE-null mice and, if so, through which predominant mechanism. METHODS Starting at the age of 6 weeks, mice received intraperitoneal injections of either 0.25 ng/g body weight of calcitriol or the vehicle, every other day for 8 weeks. RESULTS Calcitriol treatment resulted in 35% reduction of atherosclerosis at the aortic sinus, and in a significant decrease in blood pressure. These effects were possibly mediated by downregulation of the renin-angiotensin system (RAS), as there was a 64% decrease in the aortic level of renin mRNA. None of the other components of the RAS or the prorenin receptor were affected by treatment. Low-dose calcitriol treatment did not modify the plasma level of monocyte chemoattractant protein-1, interferon γ, interleukin-4 and interleukin-10, which were similar in control and treated mice. Likewise, there was no difference in the percentage of splenic Foxp3+ regulatory T cells. Calcitriol treatment resulted in an unfavorable metabolic profile (glucose and lipids), as determined after a limited fast, a difference that disappeared after food was withheld for a longer time. CONCLUSIONS At a relatively low dosage, calcitriol attenuates the development of atherosclerosis in apoE-null mice, most probably by down regulation of RAS, and not through immunomodulation; however, even at this low dose, calcitriol appears to elevate calcium and to have potentially adverse metabolic effects. Exploring the potential antiatherogenic effects of non-calcemic and safer analogues is therefore warranted.
Collapse
Affiliation(s)
- Maya Ish-Shalom
- The Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Israel
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Darabian S, Rattanasompattikul M, Hatamizadeh P, Bunnapradist S, Budoff MJ, Kovesdy CP, Kalantar-Zadeh K. Cardiorenal syndrome and vitamin D receptor activation in chronic kidney disease. Kidney Res Clin Pract 2012; 31:12-25. [PMID: 26889405 PMCID: PMC4715094 DOI: 10.1016/j.krcp.2011.12.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2011] [Revised: 11/22/2011] [Accepted: 11/22/2011] [Indexed: 02/05/2023] Open
Abstract
Cardiorenal syndrome (CRS) refers to a constellation of conditions whereby heart and kidney diseases are pathophysiologically connected. For clinical purposes, it would be more appropriate to emphasize the pathophysiological pathways to classify CRS into: (1) hemodynamic, (2) atherosclerotic, (3) uremic, (4) neurohumoral, (5) anemic–hematologic, (6) inflammatory–oxidative, (7) vitamin D receptor (VDR) and/or FGF23-, and (8) multifactorial CRS. In recent years, there have been a preponderance data indicating that vitamin D and VDR play an important role in the combination of renal and cardiac diseases. This review focuses on some important findings about VDR activation and its role in CRS, which exists frequently in chronic kidney disease patients and is a main cause of morbidity and mortality. Pathophysiological pathways related to suboptimal or defective VDR activation may play a role in causing or aggravating CRS. VDR activation using newer agents including vitamin D mimetics (such as paricalcitol and maxacalcitol) are promising agents, which may be related to their selectivity in activating VDR by means of attracting different post-D-complex cofactors. Some, but not all, studies have confirmed the survival advantages of D-mimetics as compared to non-selective VDR activators. Higher doses of D-mimetic per unit of parathyroid hormone (paricalcitol to parathyroid hormone ratio) is associated with greater survival, and the survival advantages of African American dialysis patients could be explained by higher doses of paricalcitol (>10 μg/week). More studies are needed to verify these data and to explore additional avenues for CRS management via modulating VDR pathway.
Collapse
Affiliation(s)
- Sirous Darabian
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA; St. John Cardiovascular Reserach Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
| | - Manoch Rattanasompattikul
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
| | - Parta Hatamizadeh
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
| | | | - Matthew J Budoff
- St. John Cardiovascular Reserach Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
| | | | - Kamyar Kalantar-Zadeh
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; UCLA School of Public Health, Los Angeles, CA, USA
| |
Collapse
|
|
49
|
Taddei S, Nami R, Bruno RM, Quatrini I, Nuti R. Hypertension, left ventricular hypertrophy and chronic kidney disease. Heart Fail Rev 2012; 16:615-20. [PMID: 21116711 DOI: 10.1007/s10741-010-9197-z] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Left ventricular hypertrophy (LVH) is a cardiovascular complication highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease. LVH in CKD patients has generally a negative prognostic value, because it represents an independent risk factor for the development of arrhythmias, sudden death, heart failure and ischemic heart disease. LVH in CKD patients is secondary to both pressure and volume overload. Pressure overload is secondary to preexisting hypertension, but also to a loss of elasticity of the vessels and to vascular calcifications, leading to augmented pulse pressure. Anemia and the retention of sodium and water secondary to decreased renal function are responsible for volume overload, determining a hyperdynamic state. In particular, the correction of anemia with erythropoietin in CKD patients is advantageous, since it determines LVH reduction. Other risk factors for LVH in CKD patients are documented: some are specific to CKD, as mineral metabolism disorders (hypocalcemia, hyperphosphatemia, low serum vitamin D levels and secondary hyperparathyroidism), others are non-traditional, such as increased asymmetric dimethylarginine, oxidative stress, hyperhomocysteinemia and endothelial dysfunction that, in turn, accelerates the process of atherogenesis, triggers the inflammation and pro-thrombotic state of the glomerular and the vascular endothelium and aggravates the process of both CKD and LVH.
Collapse
Affiliation(s)
- Stefano Taddei
- Department of Internal Medicine, University of Pisa, Pisa, Italy
| | | | | | | | | |
Collapse
|
|
50
|
Lee JI, Oh SJ, Ha WC, Kwon HS, Sohn TS, Son HS, Cha BY. Serum 25-hydroxyvitamin D concentration and arterial stiffness among type 2 diabetes. Diabetes Res Clin Pract 2012; 95:42-7. [PMID: 21963093 DOI: 10.1016/j.diabres.2011.09.006] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2011] [Revised: 08/25/2011] [Accepted: 09/05/2011] [Indexed: 10/17/2022]
Abstract
AIM To evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] and arterial stiffness in patients with type 2 diabetes. METHODS Serum 25(OH)D was measured in a cross-sectional sample of 131 men and 174 women aged 30 years and over in Korea. Arterial stiffness was assessed by pulse wave velocity (PWV) obtained with a VP-2000 pulse wave unit. Fasting plasma glucose, insulin, lipid profile, HbA1c, calcium, phosphorous, and HS-CRP were measured. RESULTS The prevalence of vitamin D deficiency was high (85.9%). Those with lower vitamin D levels had increased PWV. Using multivariate regression analysis, low 25(OH)D concentrations independently predicted PWV (p<0.001) in people with type 2 diabetes after adjustment for other risk factors such as age, smoking, hypertension, HS-CRP, diabetes duration, hypertension duration, HbA1c, and BMI. CONCLUSIONS Vitamin D deficiency is common in type 2 diabetes, and a low 25(OH)D level is significantly associated with increased arterial stiffness in these patients. Vitamin D may influence the development of cardiovascular disease. Clinical intervention studies are needed to clarify whether treatment with vitamin D decreases the risk of cardiovascular disease in patients with type 2 diabetes.
Collapse
Affiliation(s)
- Jee-In Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea
| | | | | | | | | | | | | |
Collapse
|