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Eichhorn L, Kleiner JL, Bartsch B, Nazir MLF, Zhang Y, Coburn M, Frede S, Weisheit CK. CCR2 dependent recruited pro-inflammatory monocytes contribute to the development of left ventricular hypertrophy in mice upon transverse aortic constriction. PLoS One 2025; 20:e0318407. [PMID: 40257974 PMCID: PMC12011267 DOI: 10.1371/journal.pone.0318407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 01/15/2025] [Indexed: 04/23/2025] Open
Abstract
C-C chemokine receptor type 2 positive monocytes are recruited from the circulation to infiltrate inflamed tissue. Left ventricular (LV) hypertrophy caused by pressure overload presents with a chronic myocardial inflammation in our mouse model of transverse aortic constriction (TAC). Recent analyses demonstrated that deficiency of fractalkine receptor CX3CR1 leads to a pro-inflammatory phenotype characterized by increased numbers of Ly6Chigh macrophages in the myocardium due to chemokine receptor CCR2 dependent monocyte recruitment from the circulation. Here, we analyzed the role of CCR2 in the development of left ventricular hypertrophy using Ccr2-/- mice. We were able to show that a lack of CCR2 dependent recruited Ly6Chigh monocytes in the myocardium reveled cardioprotective effects resulting in less hypertrophy and reduced brain natriuretic peptide (BNP) expression, as biomarker of heart failure, in the myocardium. CCR2-deficiency caused an increase in neutrophil and a reduced macrophage accumulation in the myocardium in response to pressure overload. The cytokine pattern measured in the LV tissue indicates a significantly reduced release of IL1-β whereas TNF-α concentrations are increased following TAC. IL-6 secretion is not altered by the lack of CCR2 and the pro-remodeling cytokine IL-10 is not increased either. This study highlights the importance of CCR2 in the pathogenesis of LV hypertrophy and the relevance of CCR2 dependent recruited monocytes for the orchestration of the cardiac immune response.
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MESH Headings
- Animals
- Receptors, CCR2/metabolism
- Receptors, CCR2/genetics
- Hypertrophy, Left Ventricular/metabolism
- Hypertrophy, Left Ventricular/pathology
- Hypertrophy, Left Ventricular/etiology
- Hypertrophy, Left Ventricular/genetics
- Hypertrophy, Left Ventricular/immunology
- Monocytes/metabolism
- Monocytes/pathology
- Monocytes/immunology
- Mice
- Mice, Knockout
- Male
- Macrophages/metabolism
- Myocardium/metabolism
- Myocardium/pathology
- Aorta/pathology
- Natriuretic Peptide, Brain/metabolism
- Mice, Inbred C57BL
- Disease Models, Animal
- Inflammation/pathology
- Cytokines/metabolism
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Affiliation(s)
- Lars Eichhorn
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
- Department of Anesthesiology, Helios Klinikum Bonn/Rhein-Sieg, Bonn, Germany
| | - Jan Lukas Kleiner
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
| | - Benedikt Bartsch
- Heart Center Bonn, Department of Medicine II, University Hospital Bonn, Bonn, Germany
| | - Mariam Louis Fathy Nazir
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
| | - Yunyang Zhang
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
| | - Mark Coburn
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
| | - Stilla Frede
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
| | - Christina Katharina Weisheit
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
- Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, University of Cologne, University Hospital Cologne, Cologne, Germany
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2
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Liu X, Li B, Wang S, Zhang E, Schultz M, Touma M, Monteiro Da Rocha A, Evans SM, Eichmann A, Herron T, Chen R, Xiong D, Jaworski A, Weiss S, Si MS. Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy. Circ Res 2024; 134:913-930. [PMID: 38414132 PMCID: PMC10977056 DOI: 10.1161/circresaha.122.321292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 02/08/2024] [Accepted: 02/12/2024] [Indexed: 02/29/2024]
Abstract
BACKGROUND Recently shown to regulate cardiac development, the secreted axon guidance molecule SLIT3 maintains its expression in the postnatal heart. Despite its known expression in the cardiovascular system after birth, SLIT3's relevance to cardiovascular function in the postnatal state remains unknown. As such, the objectives of this study were to determine the postnatal myocardial sources of SLIT3 and to evaluate its functional role in regulating the cardiac response to pressure overload stress. METHODS We performed in vitro studies on cardiomyocytes and myocardial tissue samples from patients and performed in vivo investigation with SLIT3 and ROBO1 (roundabout homolog 1) mutant mice undergoing transverse aortic constriction to establish the role of SLIT3-ROBO1 in adverse cardiac remodeling. RESULTS We first found that SLIT3 transcription was increased in myocardial tissue obtained from patients with congenital heart defects that caused ventricular pressure overload. Immunostaining of hearts from WT (wild-type) and reporter mice revealed that SLIT3 is secreted by cardiac stromal cells, namely fibroblasts and vascular mural cells, within the heart. Conditioned media from cardiac fibroblasts and vascular mural cells both stimulated cardiomyocyte hypertrophy in vitro, an effect that was partially inhibited by an anti-SLIT3 antibody. Also, the N-terminal, but not the C-terminal, fragment of SLIT3 and the forced overexpression of SLIT3 stimulated cardiomyocyte hypertrophy and the transcription of hypertrophy-related genes. We next determined that ROBO1 was the most highly expressed roundabout receptor in cardiomyocytes and that ROBO1 mediated SLIT3's hypertrophic effects in vitro. In vivo, Tcf21+ fibroblast and Tbx18+ vascular mural cell-specific knockout of SLIT3 in mice resulted in decreased left ventricular hypertrophy and cardiac fibrosis after transverse aortic constriction. Furthermore, α-MHC+ cardiomyocyte-specific deletion of ROBO1 also preserved left ventricular function and abrogated hypertrophy, but not fibrosis, after transverse aortic constriction. CONCLUSIONS Collectively, these results indicate a novel role for the SLIT3-ROBO1-signaling axis in regulating postnatal cardiomyocyte hypertrophy induced by pressure overload.
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Affiliation(s)
- Xiaoxiao Liu
- Department of Cardiac Surgery (X.L., B.L., S.W., D.X., M.-S.S.), Michigan Medicine, Ann Arbor
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, China (X.L., R.C.)
| | - Baolei Li
- Department of Cardiac Surgery (X.L., B.L., S.W., D.X., M.-S.S.), Michigan Medicine, Ann Arbor
- Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, China (B.L.)
| | - Shuyun Wang
- Department of Cardiac Surgery (X.L., B.L., S.W., D.X., M.-S.S.), Michigan Medicine, Ann Arbor
| | - Erge Zhang
- Division of Cardiac Surgery, Department of Surgery (E.Z., M.S., M.-S.S.), David Geffen School of Medicine University of California, Los Angeles
| | - Megan Schultz
- Division of Cardiac Surgery, Department of Surgery (E.Z., M.S., M.-S.S.), David Geffen School of Medicine University of California, Los Angeles
| | - Marlin Touma
- Department of Pediatrics (M.T.), David Geffen School of Medicine University of California, Los Angeles
| | - Andre Monteiro Da Rocha
- Division of Cardiovascular Medicine, Department of Internal Medicine (A.M.D.R., T.H.), Michigan Medicine, Ann Arbor
| | - Sylvia M. Evans
- Skaggs School of Pharmacy and Pharmaceutical Sciences (S.M.E.), University of California, San Diego, La Jolla
- Department of Medicine, School of Medicine (S.M.E.), University of California, San Diego, La Jolla
| | - Anne Eichmann
- Department of Internal Medicine, Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT (A.E.)
- INSERM, Paris Cardiovascular Research Center (PARCC), Université de Paris, France (A.E.)
| | - Todd Herron
- Division of Cardiovascular Medicine, Department of Internal Medicine (A.M.D.R., T.H.), Michigan Medicine, Ann Arbor
| | - Ruizhen Chen
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, China (X.L., R.C.)
| | - Dingding Xiong
- Department of Cardiac Surgery (X.L., B.L., S.W., D.X., M.-S.S.), Michigan Medicine, Ann Arbor
| | - Alexander Jaworski
- Division of Biology and Medicine, Department of Neuroscience, Brown University, Providence, RI (A.J.)
| | - Stephen Weiss
- Life Sciences Institute, University of Michigan, Ann Arbor (S.W.)
| | - Ming-Sing Si
- Department of Cardiac Surgery (X.L., B.L., S.W., D.X., M.-S.S.), Michigan Medicine, Ann Arbor
- Division of Cardiac Surgery, Department of Surgery (E.Z., M.S., M.-S.S.), David Geffen School of Medicine University of California, Los Angeles
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Zhou H, Zhang H, Zhan Q, Bai Y, Liu S, Yang X, Li J, Ma Z, Huang X, Zeng Q, Ren H, Xu D. Blood pressure trajectories in early adulthood and myocardial structure and function in later life. ESC Heart Fail 2022; 9:1258-1268. [PMID: 35049140 PMCID: PMC8934963 DOI: 10.1002/ehf2.13803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 11/24/2021] [Accepted: 12/28/2021] [Indexed: 11/06/2022] Open
Affiliation(s)
- Haobin Zhou
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital Southern Medical University 1838 North Guangzhou Avenue Guangzhou Guangdong 510515 China
| | - Hao Zhang
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital Southern Medical University 1838 North Guangzhou Avenue Guangzhou Guangdong 510515 China
| | - Qiong Zhan
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital Southern Medical University 1838 North Guangzhou Avenue Guangzhou Guangdong 510515 China
| | - Yujia Bai
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital Southern Medical University 1838 North Guangzhou Avenue Guangzhou Guangdong 510515 China
| | - Shenrong Liu
- Department of Cardiac Pediatrics, Guangdong Cardiovascular Institute Guangdong Academy of Medical Sciences/Guangdong General Hospital Guangzhou China
| | - Xi Yang
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital Southern Medical University 1838 North Guangzhou Avenue Guangzhou Guangdong 510515 China
| | - Jiaying Li
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital Southern Medical University 1838 North Guangzhou Avenue Guangzhou Guangdong 510515 China
| | - Zhuang Ma
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital Southern Medical University 1838 North Guangzhou Avenue Guangzhou Guangdong 510515 China
| | - Xingfu Huang
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital Southern Medical University 1838 North Guangzhou Avenue Guangzhou Guangdong 510515 China
| | - Qingchun Zeng
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital Southern Medical University 1838 North Guangzhou Avenue Guangzhou Guangdong 510515 China
| | - Hao Ren
- Department of Rheumatology, Nanfang Hospital Southern Medical University 1838 Northern Guangzhou Avenue Guangzhou Guangdong 510515 China
| | - Dingli Xu
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital Southern Medical University 1838 North Guangzhou Avenue Guangzhou Guangdong 510515 China
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Álvarez-Aliaga A, Frómeta-Guerra A, Suárez-Quesada A, Del Llano-Sosa D, Berdú-Saumell J, Lago-Santiesteban YA. Prognostic model of the adaptive changes from hypertensive cardiopathy: from mild diastolic dysfunction to depressed systolic function. Medwave 2020; 20:e7873. [PMID: 32469849 DOI: 10.5867/medwave.2020.03.7873] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 03/18/2020] [Indexed: 11/27/2022] Open
Abstract
Introduction By definition, hypertensive cardiopathy is a series of complex and variable effects responsible for the chronic elevation of blood pressure in the heart. It stands out within a broad spectrum of cardiovascular diseases associated with hypertension. Objective To evaluate the capacity to predict the development of adaptive changes to hypertensive cardiopathy within ten years following diagnosis of the condition, using a model based on prognostic factors. Methods A prospective cohort study was conducted in hypertensive patients. The patients were followed at the specialized hypertension physicians office of the specialty policlinic attached to Carlos Manuel de Céspedes University Hospital, in the Bayamo Municipality, Granma Province, Cuba, from 1 January 2008 to 31 December 2018. Results Coxs proportional regression model showed a significant statistical relationship between most of the factors and the development of the adaptive changes in hypertensive cardiopathy within ten years of follow-up after the diagnosis of this condition. The lack of blood pressure control (Hazard ratio: 2.090; confidence interval 95%: 1.688 to 2.588; p: 0.000) followed by stage 2 of hypertension (hazard ratio: 1.987; confidence interval 95%: 1.584 to 2.491; p: 0.000) were the main factors. Internal validation of the model, discriminant capacity (C- statistic: 0.897) and calibration Hosmer-Lemeshow (χ2: 5.384; p: 0.716), was acceptable. Conclusions We develop a model to predict the progression of hypertensive cardiopathy from grade I to grade IV with adequate discriminatory capacity. The model is based on prognostic factors, among which characteristic effects of arterial hypertension, diabetes mellitus, and chronic kidney disease stood out.
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Affiliation(s)
- Alexis Álvarez-Aliaga
- Hospital General Universitario Carlos Manuel de Céspedes, Bayamo, Granma, Cuba. Universidad de Ciencias Médicas de Granma, Bayamo, Cuba. . ORCID: 0000-0002-4706-3821
| | - Adonis Frómeta-Guerra
- Hospital General Universitario Carlos Manuel de Céspedes, Bayamo, Granma, Cuba. Universidad de Ciencias Médicas de Granma, Bayamo, Cuba. ORCID: 0000-0003-0436-5974
| | - Alexis Suárez-Quesada
- Hospital General Universitario Carlos Manuel de Céspedes, Bayamo, Granma, Cuba. Universidad de Ciencias Médicas de Granma, Bayamo, Cuba. ORCID: 0000-0002-7672-5601
| | - David Del Llano-Sosa
- Hospital General Universitario Carlos Manuel de Céspedes, Bayamo, Granma, Cuba. Universidad de Ciencias Médicas de Granma, Bayamo, Cuba. ORCID: 0000-0002-0104-1715
| | - Joel Berdú-Saumell
- Hospital General Universitario Carlos Manuel de Céspedes, Bayamo, Granma, Cuba. Universidad de Ciencias Médicas de Granma, Bayamo, Cuba. ORCID: 0000-0002-8818-2704
| | - Yasel Alberto Lago-Santiesteban
- Hospital General Universitario Carlos Manuel de Céspedes, Bayamo, Granma, Cuba. Universidad de Ciencias Médicas de Granma, Bayamo, Cuba. ORCID: 0000-0003-2933-0663
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Wang C, Koo S, Park M, Vangelatos Z, Hoang P, Conklin B, Grigoropoulos CP, Healy KE, Ma Z. Maladaptive Contractility of 3D Human Cardiac Microtissues to Mechanical Nonuniformity. Adv Healthc Mater 2020; 9:e1901373. [PMID: 32090507 PMCID: PMC7274862 DOI: 10.1002/adhm.201901373] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 02/01/2020] [Indexed: 01/29/2023]
Abstract
Cardiac tissues are able to adjust their contractile behavior to adapt to the local mechanical environment. Nonuniformity of the native tissue mechanical properties contributes to the development of heart dysfunctions, yet the current in vitro cardiac tissue models often fail to recapitulate the mechanical nonuniformity. To address this issue, a 3D cardiac microtissue model is developed with engineered mechanical nonuniformity, enabled by 3D-printed hybrid matrices composed of fibers with different diameters. When escalating the complexity of tissue mechanical environments, cardiac microtissues start to develop maladaptive hypercontractile phenotypes, demonstrated in both contractile motion analysis and force-power analysis. This novel hybrid system could potentially facilitate the establishment of "pathologically-inspired" cardiac microtissue models for deeper understanding of heart pathology due to nonuniformity of the tissue mechanical environment.
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Affiliation(s)
- Chenyan Wang
- Department of Biomedical & Chemical Engineering, Syracuse Biomaterials Institute, Syracuse University
| | - Sangmo Koo
- Department of Mechanical Engineering, University of California, Berkeley
| | - Minok Park
- Department of Mechanical Engineering, University of California, Berkeley
| | | | - Plansky Hoang
- Department of Biomedical & Chemical Engineering, Syracuse Biomaterials Institute, Syracuse University
| | - Bruce Conklin
- Gladstone Institute of Cardiovascular Diseases, University of California, San Francisco
| | | | - Kevin E. Healy
- Department of Bioengineering, University of California, Berkeley
- Department of Material Science & Engineering, University of California, Berkeley
| | - Zhen Ma
- Department of Biomedical & Chemical Engineering, Syracuse Biomaterials Institute, Syracuse University
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Di Mattia RA, Mariángelo JI, Blanco PG, Jaquenod De Giusti C, Portiansky EL, Mundiña-Weilenmann C, Aiello EA, Orlowski A. The activation of the G protein-coupled estrogen receptor (GPER) prevents and regresses cardiac hypertrophy. Life Sci 2020; 242:117211. [DOI: 10.1016/j.lfs.2019.117211] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 12/06/2019] [Accepted: 12/18/2019] [Indexed: 12/25/2022]
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Brea MS, Díaz RG, Escudero DS, Zavala MR, Portiansky EL, Villa-Abrille MC, Caldiz CI, Pérez NG, Morgan PE. Silencing of epidermal growth factor receptor reduces Na+/H+ exchanger 1 activity and hypertensive cardiac hypertrophy. Biochem Pharmacol 2019; 170:113667. [DOI: 10.1016/j.bcp.2019.113667] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 10/11/2019] [Indexed: 02/06/2023]
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High Normal Blood Pressure and Left Ventricular Hypertrophy Echocardiographic Findings From the PAMELA Population. Hypertension 2019; 73:612-619. [DOI: 10.1161/hypertensionaha.118.12114] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Urinary sodium excretion and risk of cardiovascular disease in the Chinese population: a prospective study. Hypertens Res 2018; 41:849-855. [DOI: 10.1038/s41440-018-0091-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 01/25/2018] [Accepted: 02/27/2018] [Indexed: 11/08/2022]
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10
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Cao JL, Yang YQ, Nabeel DM, Sun YL, Zou HYY, Kong XQ, Lu XZ. Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy in Hypertensive Patients and Its Clinical Significance. Cardiology 2018; 139:124-131. [PMID: 29332066 DOI: 10.1159/000481280] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 08/18/2017] [Indexed: 11/19/2022]
Abstract
OBJECTIVE The aim of this study is to investigate the correlation between calcineurin (CaN) and hypertension with left ventricular hypertrophy (HLVH) and to evaluate its potential clinical significance. DESIGN The study involved 160 patients diagnosed with hypertension and 42 controls. Based on the exclusion criteria, 42 were not eligible for this study. The remaining 118 hypertensive patients were categorized into 2 subgroups based on left ventricular mass index and relative ventricular wall thickness: a normal model subgroup with hypertension (HNM) and an HLVH subgroup. Serum CaN levels were determined by enzyme-linked immunosorbent assay, while serum CaN activity was determined by malachite green colorimetric assay. RESULTS Among the HNM and HLVH subgroups, a positive correlation was demonstrated between serum CaN activity, but not serum CaN level, and HLVH. Moreover, the HLVH subgroup displayed a remarkable increase in the levels of brain natriuretic peptide, cystatin C, urinary albumin/creatinine ratio, and left atrium diameter compared to the HNM subgroup and controls. CONCLUSION There was a positive correlation between serum CaN activity and LVH in hypertensive patients. Activated CaN could play an important role in the pathophysiologic mechanism of HLVH. Serum CaN activity could be a clinically useful diagnostic and prognostic biomarker for LVH.
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Affiliation(s)
- Jia-Li Cao
- Department of Cardiology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China
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11
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Zhou N, Ma B, Stoll S, Hays TT, Qiu H. The valosin-containing protein is a novel repressor of cardiomyocyte hypertrophy induced by pressure overload. Aging Cell 2017; 16:1168-1179. [PMID: 28799247 PMCID: PMC5595673 DOI: 10.1111/acel.12653] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/01/2017] [Indexed: 12/22/2022] Open
Abstract
Hypertension‐induced left ventricular hypertrophy (LVH) is an independent risk factor for heart failure. Regression of LVH has emerged as a major goal in the treatment of hypertensive patients. Here, we tested our hypothesis that the valosin‐containing protein (VCP), an ATPase associate protein, is a novel repressor of cardiomyocyte hypertrophy under the pressure overload stress. Left ventricular hypertrophy (LVH) was determined by echocardiography in 4‐month male spontaneously hypertensive rats (SHRs) vs. age‐matched normotensive Wistar Kyoto (WKY) rats. VCP expression was found to be significantly downregulated in the left ventricle (LV) tissues from SHRs vs. WKY rats. Pressure overload was induced by transverse aortic constriction (TAC) in wild‐type (WT) mice. At the end of 2 weeks, mice with TAC developed significant LVH whereas the cardiac function remained unchanged. A significant reduction of VCP at both the mRNA and protein levels in hypertrophic LV tissue was found in TAC WT mice compared to sham controls. Valosin‐containing protein VCP expression was also observed to be time‐ and dose‐dependently reduced in vitro in isolated neonatal rat cardiomyocytes upon the treatment of angiotensin II. Conversely, transgenic (TG) mice with cardiac‐specific overexpression of VCP showed a significant repression in TAC‐induced LVH vs. litter‐matched WT controls upon 2‐week TAC. TAC‐induced activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling observed in WT mice LVs was also significantly blunted in VCP TG mice. In conclusion, VCP acts as a novel repressor that is able to prevent cardiomyocyte hypertrophy from pressure overload by modulating the mTORC1 signaling pathway.
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Affiliation(s)
- Ning Zhou
- Division of Cardiology; Department of Internal Medicine; Tongji Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan China
- Division of Physiology; Department of Basic Sciences; School of Medicine; Loma Linda University; Loma Linda CA USA
| | - Ben Ma
- Division of Physiology; Department of Basic Sciences; School of Medicine; Loma Linda University; Loma Linda CA USA
| | - Shaunrick Stoll
- Division of Physiology; Department of Basic Sciences; School of Medicine; Loma Linda University; Loma Linda CA USA
| | - Tristan T. Hays
- Division of Physiology; Department of Basic Sciences; School of Medicine; Loma Linda University; Loma Linda CA USA
| | - Hongyu Qiu
- Division of Physiology; Department of Basic Sciences; School of Medicine; Loma Linda University; Loma Linda CA USA
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12
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Tereshchenko LG, Soliman EZ, Davis BR, Oparil S. Risk stratification of sudden cardiac death in hypertension. J Electrocardiol 2017; 50:798-801. [PMID: 28916176 DOI: 10.1016/j.jelectrocard.2017.08.012] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Indexed: 12/28/2022]
Abstract
In the United States, up to 450,000 people per year die suddenly; an average of 1 sudden death every 70s. Strategies for preventing sudden cardiac death are urgently needed. Systemic arterial hypertension is a major risk factor for sudden cardiac death and the increasing burden of hypertension is a worldwide problem. The lifetime risk of sudden cardiac death at 30years of age is higher by 30% in individuals with hypertension. Each 20/10mmHg increase in systolic/diastolic blood pressure, is associated with a 20% additional increase in sudden cardiac death risk. Theoretically, antihypertensive treatment should be an effective strategy for sudden cardiac death prevention. However, a recent meta-analysis of 15 randomized controlled trials showed that antihypertensive treatment does not reduce the incidence of sudden cardiac death. This manuscript reviews ECG predictors of sudden cardiac death and the importance of risk stratification for appropriate management of hypertension.
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Affiliation(s)
- Larisa G Tereshchenko
- The Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, United States.
| | - Elsayed Z Soliman
- Epidemiological Cardiology Research Center (EPICARE), Division of Public Health Sciences, Department of Medicine, Cardiology Section, Wake Forest School of Medicine, Winston Salem, NC, United States
| | - Barry R Davis
- University of Texas School of Public Health, Houston, TX, United States
| | - Suzanne Oparil
- University of Alabama at Birmingham, Department of Medicine, School of Medicine, Birmingham, AL, United States
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13
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The Effects of Guizhi Gancao Decoction on Pressure Overload-Induced Heart Failure and Posttranslational Modifications of Tubulin in Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 2017:2915247. [PMID: 28798797 PMCID: PMC5536145 DOI: 10.1155/2017/2915247] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2017] [Accepted: 06/13/2017] [Indexed: 11/17/2022]
Abstract
Guizhi Gancao Decoction (GGD), a traditional Chinese medical recipe, has been widely used in the treatment of cardiovascular diseases in China for centuries. The present study was carried out to determine whether GGD exerts direct protective effects against pressure overload-induced heart failure. Moreover, we investigated whether GGD affects tubulin expression and posttranslational modifications. We demonstrated that GGD ameliorated TAC caused cardiac hypertrophy by gravimetric and echocardiography analysis in C57BL/6 mice. We found that GGD abrogated TAC-induced myocardium fibrosis by Masson's staining and collagen volume fraction (CVF) analysis. By using pressure-volume hemodynamic measurements, we found that GGD prevented TAC-induced cardiac systolic and diastolic dysfunction. Immunoblotting and immunofluorescent analysis revealed that GGD abrogated TAC-induced detyrosination and acetylation abnormalities on microtubules. Our present study demonstrated potential therapeutic effects of GGD against pressure overload-induced heart failure.
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14
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Piontek K, Schmidt CO, Baumeister SE, Lerch MM, Mayerle J, Dörr M, Felix SB, Völzke H. Is hepatic steatosis associated with left ventricular mass index increase in the general population? World J Hepatol 2017; 9:857-866. [PMID: 28740597 PMCID: PMC5504361 DOI: 10.4254/wjh.v9.i19.857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 12/31/2016] [Accepted: 04/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the association between hepatic steatosis and change in left ventricular mass index (LVMI) over five years, and examine whether systolic and diastolic blood pressures are mediators of the association between hepatic steatosis and LVMI using a general population sample.
METHODS We analyzed data from the Study of Health in Pomerania. The study population comprised 1298 individuals aged 45 to 81 years. Hepatic steatosis was defined as the presence of a hyperechogenic pattern of the liver together with elevated serum alanine transferase levels. Left ventricular mass was determined echocardiographically and indexed to height2.7. Path analyses were conducted to differentiate direct and indirect paths from hepatic steatosis to LVMI encompassing systolic and diastolic blood pressure as potential mediating variables.
RESULTS Hepatic steatosis was a significant predictor for all measured echocardiographic characteristics at baseline. Path analyses revealed that the association of hepatic steatosis with LVMI change after five years was negligibly small (β = -0.12, s.e. = 0.21, P = 0.55). Systolic blood pressure at baseline was inversely associated with LVMI change (β = -0.09, s.e. = 0.03, P < 0.01), while no association between diastolic blood pressure at baseline and LVMI change was evident (β = 0.03, s.e. = 0.05, P = 0.56). The effect of the indirect path from hepatic steatosis to LVMI via systolic baseline blood pressure was small (β = -0.20, s.e. = 0.10, P = 0.07). No indirect effect was observed for the path via diastolic baseline blood pressure (β = 0.03, s.e. = 0.06, P = 0.60). Similar associations were observed in the subgroup of individuals not receiving beta-blockers, calcium channel blockers, or drugs acting on the renin-angiotensin system.
CONCLUSION Baseline associations between hepatic steatosis and LVMI do not extend to associations with LVMI change after five years. More studies are needed to study the longitudinal effects of hepatic steatosis on LVMI.
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Georgakis MK, Synetos A, Mihas C, Karalexi MA, Tousoulis D, Seshadri S, Petridou ET. Left ventricular hypertrophy in association with cognitive impairment: a systematic review and meta-analysis. Hypertens Res 2017; 40:696-709. [PMID: 28202945 DOI: 10.1038/hr.2017.11] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 12/03/2016] [Accepted: 12/21/2016] [Indexed: 02/06/2023]
Abstract
Left ventricular hypertrophy (LVH) is a marker of prolonged exposure to high blood pressure and a predictor of cardiovascular disease risk. The objective of the current study was to investigate its association with cognitive function. Following standard guidelines, pairs of independent reviewers screened 2359 articles to search for studies that addressed the research question, extracted data and evaluated the quality of the studies using the Newcastle-Ottawa scale; authors were contacted for additional data. A random-effects meta-analysis and a meta-regression analysis were performed. Eighteen eligible studies using various methodologies and of varying quality were identified. However, both cross-sectional and prospective studies were indicative of a positive association between LVH and cognitive impairment or cognitive performance and decline in both population-based and patient-based subjects. The meta-analysis showed an increased risk of cognitive impairment among subjects with LVH in population-based studies (9 studies; 28 648 subjects; odds ratio (OR): 1.40, 95% confidence interval (CI): 1.18-1.66) and studies exclusively on hypertensive subjects (3 studies; 1262 subjects; OR: 2.14, 95% CI: 1.39-3.30). The effect was stronger when assessing LVH by echocardiography rather than electrocardiogram and was retained in the sensitivity analyses of prospective and highest quality studies and studies adjusting for hypertension or blood pressure levels. No heterogeneity or publication bias was documented, whereas the presence of hypertension seemed to reinforce the reported association, as derived from the meta-regression analysis. There is evidence suggesting an independent association of LVH with cognitive impairment. Because of the highly heterogeneous methodologies, future large prospective studies with clinically defined dementia outcomes are needed to replicate the findings.
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Affiliation(s)
- Marios K Georgakis
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Andreas Synetos
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
- First Department of Cardiology, Hippokrateion Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Constantinos Mihas
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria A Karalexi
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Tousoulis
- First Department of Cardiology, Hippokrateion Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Sudha Seshadri
- Department of Neurology, Boston University School of Medicine, Boston, MA, USA
| | - Eleni Th Petridou
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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Moreno MU, Eiros R, Gavira JJ, Gallego C, González A, Ravassa S, López B, Beaumont J, San José G, Díez J. The Hypertensive Myocardium: From Microscopic Lesions to Clinical Complications and Outcomes. Med Clin North Am 2017; 101:43-52. [PMID: 27884234 DOI: 10.1016/j.mcna.2016.08.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The chronic hemodynamic load imposed by hypertension on the left ventricle leads to lesions in the myocardium that result in structural remodeling, which provides support for alterations in cardiac function, perfusion, and electrical activity that adversely influence the clinical evolution of hypertensive heart disease. Management must include detecting, reducing, and reversing left ventricular hypertrophy, as well as the detection and repair of microscopic lesions responsible for myocardial remodeling. Reducing the burden associated with hypertensive heart disease can be targeted using personalized treatment. The noninvasive, biomarker-mediated identification of subsets of patients with hypertensive heart disease is essential to provide personalized treatment.
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Affiliation(s)
- María U Moreno
- Program of Cardiovascular Diseases, Center of Applied Medical Research, University of Navarra, Edificio CIMA, Av. Pío XII, 55, Pamplona 31008, Spain; IdiSNA, Navarra Institute for Health Resarch, Pamplona, Spain
| | - Rocío Eiros
- Department of Cardiology and Cardiac Surgery, University Clinic, University of Navarra, Av. Pío XII, 36, Pamplona 31008, Spain
| | - Juan J Gavira
- Department of Cardiology and Cardiac Surgery, University Clinic, University of Navarra, Av. Pío XII, 36, Pamplona 31008, Spain; IdiSNA, Navarra Institute for Health Resarch, Pamplona, Spain
| | - Catalina Gallego
- Program of Cardiovascular Diseases, Center of Applied Medical Research, University of Navarra, Edificio CIMA, Av. Pío XII, 55, Pamplona 31008, Spain; Programa de Cardiología Clínica, Clínica CardioVID, Universidad Pontificia Bolivariana, Calle 78B 75-21, Medellín, Colombia
| | - Arantxa González
- Program of Cardiovascular Diseases, Center of Applied Medical Research, University of Navarra, Edificio CIMA, Av. Pío XII, 55, Pamplona 31008, Spain; IdiSNA, Navarra Institute for Health Resarch, Pamplona, Spain
| | - Susana Ravassa
- Program of Cardiovascular Diseases, Center of Applied Medical Research, University of Navarra, Edificio CIMA, Av. Pío XII, 55, Pamplona 31008, Spain; IdiSNA, Navarra Institute for Health Resarch, Pamplona, Spain
| | - Begoña López
- Program of Cardiovascular Diseases, Center of Applied Medical Research, University of Navarra, Edificio CIMA, Av. Pío XII, 55, Pamplona 31008, Spain; IdiSNA, Navarra Institute for Health Resarch, Pamplona, Spain
| | - Javier Beaumont
- Program of Cardiovascular Diseases, Center of Applied Medical Research, University of Navarra, Edificio CIMA, Av. Pío XII, 55, Pamplona 31008, Spain; IdiSNA, Navarra Institute for Health Resarch, Pamplona, Spain
| | - Gorka San José
- Program of Cardiovascular Diseases, Center of Applied Medical Research, University of Navarra, Edificio CIMA, Av. Pío XII, 55, Pamplona 31008, Spain; IdiSNA, Navarra Institute for Health Resarch, Pamplona, Spain
| | - Javier Díez
- Program of Cardiovascular Diseases, Center of Applied Medical Research, University of Navarra, Edificio CIMA, Av. Pío XII, 55, Pamplona 31008, Spain; Department of Cardiology and Cardiac Surgery, University Clinic, University of Navarra, Av. Pío XII, 36, Pamplona 31008, Spain; IdiSNA, Navarra Institute for Health Resarch, Pamplona, Spain.
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17
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Cuspidi C, Facchetti R, Sala C, Bombelli M, Tadic M, Grassi G, Mancia G. Do Combined Electrocardiographic and Echocardiographic Markers of Left Ventricular Hypertrophy Improve Cardiovascular Risk Estimation? J Clin Hypertens (Greenwich) 2016; 18:846-54. [PMID: 27160298 PMCID: PMC8032070 DOI: 10.1111/jch.12834] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Revised: 01/31/2016] [Accepted: 02/08/2016] [Indexed: 11/30/2022]
Abstract
The authors estimated the risk of cardiovascular mortality associated with echocardiographic (ECHO) left ventricular hypertrophy (LVH) and subtypes of this phenotype in patients with and without electrocardiographic (ECG) LVH. A total of 1691 representatives of the general population were included in the analysis. During a follow-up of 211 months, 89 cardiovascular deaths were recorded. Compared with individuals with neither ECHO LVH nor ECG LVH, fully adjusted risk of cardiovascular mortality increased (hazard ratio [HR], 3.36; 95% confidence interval [CI], 1.51-7.47; P=.003) in patients with both ECHO-LVH and ECG-LVH, whereas the risk entailed by ECHO-LVH alone was of borderline statistical significance (P=.04). Combined concentric nondilated LVH and ECG-LVH, but not concentric nondilated LVH alone, predicted cardiovascular death (HR, 3.79; 95% CI, 1.25-11.38; P=.01). Similar findings were observed for eccentric nondilated LVH (HR, 3.37; 95% CI, 1.05-10.78; P=.04.). The present analysis underlines the value of combining ECG and ECHO in the assessment of cardiovascular prognosis related to abnormal left ventricular geometric patterns.
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Affiliation(s)
- Cesare Cuspidi
- Department of Health Science, University of Milano-Bicocca, Milano, Italy.
- Istituto Auxologico Italiano IRCCS, Milano, Italy.
| | - Rita Facchetti
- Department of Health Science, University of Milano-Bicocca, Milano, Italy
| | - Carla Sala
- Department of Clinical Sciences and Community Health, University of Milano and Fondazione Ospedale Maggiore Policlinico, Milano, Italy
| | - Michele Bombelli
- Department of Health Science, University of Milano-Bicocca, Milano, Italy
| | - Marijana Tadic
- University Clinical Hospital Centre "Dragisa Misovic", Belgrade, Serbia
| | - Guido Grassi
- Department of Health Science, University of Milano-Bicocca, Milano, Italy
- IRCCS Multimedica, Milano, Italy
| | - Giuseppe Mancia
- Department of Health Science, University of Milano-Bicocca, Milano, Italy
- Istituto Auxologico Italiano IRCCS, Milano, Italy
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18
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Hemorrhagic transformation of acute ischemic stroke is limited in hypertensive patients with cardiac hypertrophy. Int J Cardiol 2016; 219:362-6. [DOI: 10.1016/j.ijcard.2016.06.060] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 06/18/2016] [Indexed: 12/18/2022]
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Ismail B, deKemp RA, Hadizad T, Mackasey K, Beanlands RS, DaSilva JN. Decreased renal AT1 receptor binding in rats after subtotal nephrectomy: PET study with [(18)F]FPyKYNE-losartan. EJNMMI Res 2016; 6:55. [PMID: 27339045 PMCID: PMC4919198 DOI: 10.1186/s13550-016-0209-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Accepted: 06/14/2016] [Indexed: 01/13/2023] Open
Abstract
Background Significant renal mass reduction induced by 5/6 subtotal nephrectomy (Nx) is associated with a chain of events that culminates in hypertension and chronic kidney disease (CKD). Numerous studies have provided evidence for the role of angiotensin (Ang) II type 1 receptor (AT1R) in the promotion and progression of the disease; however, conflicting results were reported on intrarenal AT1R levels in CKD models. Methods Male Sprague-Dawley rats (n = 26) underwent Nx or sham operations. Animals were scanned at 8–10 weeks post-surgery with PET using the novel AT1R radioligand [18F]FPyKYNE-losartan. Radioligand binding was quantified by kidney-to-blood ratio (KBR), standard uptake value (SUV), and distribution volume (DV). After sacrifice, plasma and kidney Ang II levels were measured. Western blot and 125I-[Sar1, Ile8]Ang II autoradiography were performed to assess AT1R expression. Results At 8–10 weeks post-surgery, Nx rats developed hypertension, elevated plasma creatinine levels, left ventricle hypertrophy, increased myocardial blood flow (MBF), and reduced Ang II levels compared to shams. PET measurements displayed significant decrease in KBR (29 %), SUV (24 %), and DV (22 %) induced by Nx (p < 0.05), and these findings were confirmed by in vitro assays. Conclusions Reduced renal AT1Rs in hypertensive rats measured with [18F]FPyKYNE-losartan PET at 8–10 weeks following Nx support further use of this non-invasive approach in longitudinal studies to better understand the AT1R role in CKD progression.
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Affiliation(s)
- Basma Ismail
- National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada.,Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada
| | - Robert A deKemp
- National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada
| | - Tayebeh Hadizad
- National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada
| | - Kumiko Mackasey
- National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada
| | - Rob S Beanlands
- National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada.,Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada
| | - Jean N DaSilva
- National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada. .,Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. .,Department of Radiology, Radio-Oncology and Nuclear Medicine, University of Montreal, University of Montreal Hospital Research Centre (CRCHUM), 900 Rue Saint-Denis, Montréal, Québec, H2X 0A9, Canada.
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20
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White-coat hypertension, as defined by ambulatory blood pressure monitoring, and subclinical cardiac organ damage: a meta-analysis. J Hypertens 2016; 33:24-32. [PMID: 25380162 DOI: 10.1097/hjh.0000000000000416] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
AIM : The clinical and prognostic relevance of white-coat hypertension (WCH) has not been fully elucidated; in particular, the association of this blood pressure phenotype with suclinical organ damage remains unclear. We performed a systematic meta-analysis in order to provide a comprehensive information on cardiac structural and functional changes in WCH, as defined by ambulatory blood pressure monitoring. DESIGN Studies were identified by the following search terms: 'white-coat hypertension', 'isolated clinic hypertension', 'cardiac organ damage', 'target organ damage', 'left ventricle', 'left ventricular hypertrophy', 'cardiac hypertrophy', 'ventricular dysfunction', and 'echocardiography'. RESULTS A total of 7382 untreated adult patients (2493 normotensive, 1705 WCH, and 3184 hypertensive individuals) included in 25 studies were considered. Left ventricular mass index was higher in WCH than in normotensive patients [standardized difference in mean (SDM) 0.50, P < 0.01]; mitral E/A ratio was lower (SDM -0.27, P < 0.01) and left atrium larger (SDM 0.29, P < 0.05) in WCH than in the normotensive counterparts. Hypertensive patients showed a greater left ventricular mass index (SDM 0.42, P < 0.01), reduced E/A (SDM -0.15, P < 0.01), and larger left atrium diameter (SDM 0.27, P < 0.01) than WCH patients. CONCLUSIONS Our meta-analysis shows that alterations in cardiac structure and function in WCH patients, as defined by ambulatory blood pressure monitoring, are intermediate between sustained hypertensive patients and normotensive controls. The study supports the view that WCH should not be further considered a fully benign entity.
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21
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Klein R, Ametepe ES, Yam Y, Dwivedi G, Chow BJ. Cardiac CT assessment of left ventricular mass in mid-diastasis and its prognostic value. Eur Heart J Cardiovasc Imaging 2016; 18:95-102. [PMID: 26850628 DOI: 10.1093/ehjci/jev357] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Accepted: 12/22/2015] [Indexed: 12/11/2022] Open
Abstract
AIMS To determine the influence of cardiac motion on measurements of left ventricular (LV) mass obtained with 64-slice computed tomography (CT) and to elucidate the prognostic value of LV mass on major adverse cardiac events (MACE) and all-cause mortality. Increased LV mass has been linked with MACE. Although Cardiac CT allows measurement of LV anatomy, it is susceptible to motion artefacts often requiring image acquisition during diastasis. There is a need to understand variability in LV mass measurements across phases of the cardiac cycle, and whether mid-diastolic measurements have prognostic value. METHODS AND RESULTS The study comprised two equally sized cohorts of patients that had undergone retrospectively gated cardiac CT: patients who had MACE and/or all-cause death at follow-up and a matched (age, sex, and risk factors) event-free cohort. LV mass was measured at mid-diastole, end-diastole, and end-systole. Correlation and agreement between phases were determined. The incremental value of mid-diastolic hypertrophy (LVH) over the National Cholesterol Education Programme (NCEP) risk was performed for LV mass indices normalized to body surface area (LVMIBSA) or weight (LVMIWeight). Of 166 patients, 31.3% experienced MACE and 28.9% died of any cause (follow-up 22.9 ± 13.4 months). LV mass at all cardiac phases were strongly correlated (r > 0.94). Mean mid-diastolic LVMIBSA was higher in the cohort with events (93.7 vs. 80.7 g/m2, P= 0.008) as was LVMIWeight (2.26 vs. 1.88 g/kg, P = 0.001). LVMIBSA and LVMIWeight had prognostic value incremental to NCEP with 1.85 and 2.47 hazard ratios, respectively. CONCLUSIONS Measurement of LV mass can be obtained by cardiac CT images obtained at mid-diastasis. LV mass measurements obtained at mid-diastasis have prognostic value.
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Affiliation(s)
- Ran Klein
- Division of Nuclear Medicine, The Ottawa hospital, 1053 Carling Ave, Ottawa, ON, Canada, Canada, K1Y 4E9
| | | | - Yeung Yam
- Division of Cardiology, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, Canada K1Y 4W7
| | - Girish Dwivedi
- Division of Cardiology, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, Canada K1Y 4W7
| | - Benjamin J Chow
- Division of Cardiology, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, Canada K1Y 4W7
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22
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Hendriks EJE, Westerink J, de Jong PA, de Borst GJ, Nathoe HM, Mali WPTM, van der Graaf Y, van der Schouw YT, Beulens JW. Association of High Ankle Brachial Index With Incident Cardiovascular Disease and Mortality in a High-Risk Population. Arterioscler Thromb Vasc Biol 2015; 36:412-7. [PMID: 26715681 DOI: 10.1161/atvbaha.115.306657] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Accepted: 12/21/2015] [Indexed: 12/31/2022]
Abstract
OBJECTIVE The objective of this present study is to determine whether high ankle brachial index (ABI) as compared with ABIs within reference limits is associated with an increased incidence of cardiovascular disease (CVD) events and all-cause mortality in a high-risk population and whether this association is the same for patients with and without diabetes mellitus or prevalent CVD. APPROACH AND RESULTS Seven thousand five hundred and thirty-eight patients with ABI>0.9 and either prevalent CVD or a high risk for CVD were selected from the Second Manifestations of Arterial Disease (SMART) study. Three hundred and thirty-six participants (4.5%) had high ABI (≥1.4 or incompressible). Higher age, male sex, higher body mass index, and diabetes mellitus were associated with higher prevalences of high ABI; smoking and higher non-high-density lipoprotein levels were associated with lower prevalences of high ABI. Cox proportional hazards models were fitted assessing the association of high ABI (as compared with ABI 0.9-1.4) with the risk of myocardial infarction, stroke, cardiovascular death, the combined outcome of these 3, and total mortality (median follow-up 6.9 years). After multivariable adjustment, high ABI was associated with an increased risk of myocardial infarction (hazard ratio 1.83 [95% confidence interval 1.22-2.76]), but not with stroke (hazard ratio 0.86 [95% confidence interval 0.44-1.69]), cardiovascular (hazard ratio 1.14 [95% confidence interval 0.70-1.84]), or all-cause mortality (hazard ratio 0.95 [95% confidence interval 0.67-1.34]). Associations of high ABI with CVD outcomes tended to be stronger in patients with diabetes mellitus but without statistically significant interactions. CONCLUSIONS In a high-risk population, the presence of an ABI≥1.4 was associated with an increased risk for myocardial infarction, but not with stroke, all-cause, or vascular mortality.
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Affiliation(s)
- Eva J E Hendriks
- From the Julius Center for Health Sciences and Primary Care (E.J.E.H., Y.v.d.G., Y.T.v.d.S., J.W.B.), Department of Vascular Medicine (J.W.), Department of Radiology (P.A.d.J., W.P.Th.M.M.), Department of Vascular Surgery (G.J.d.B.), and Department of Cardiology (H.M.N.), University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jan Westerink
- From the Julius Center for Health Sciences and Primary Care (E.J.E.H., Y.v.d.G., Y.T.v.d.S., J.W.B.), Department of Vascular Medicine (J.W.), Department of Radiology (P.A.d.J., W.P.Th.M.M.), Department of Vascular Surgery (G.J.d.B.), and Department of Cardiology (H.M.N.), University Medical Center Utrecht, Utrecht, The Netherlands.
| | - Pim A de Jong
- From the Julius Center for Health Sciences and Primary Care (E.J.E.H., Y.v.d.G., Y.T.v.d.S., J.W.B.), Department of Vascular Medicine (J.W.), Department of Radiology (P.A.d.J., W.P.Th.M.M.), Department of Vascular Surgery (G.J.d.B.), and Department of Cardiology (H.M.N.), University Medical Center Utrecht, Utrecht, The Netherlands
| | - Gert J de Borst
- From the Julius Center for Health Sciences and Primary Care (E.J.E.H., Y.v.d.G., Y.T.v.d.S., J.W.B.), Department of Vascular Medicine (J.W.), Department of Radiology (P.A.d.J., W.P.Th.M.M.), Department of Vascular Surgery (G.J.d.B.), and Department of Cardiology (H.M.N.), University Medical Center Utrecht, Utrecht, The Netherlands
| | - Hendrik M Nathoe
- From the Julius Center for Health Sciences and Primary Care (E.J.E.H., Y.v.d.G., Y.T.v.d.S., J.W.B.), Department of Vascular Medicine (J.W.), Department of Radiology (P.A.d.J., W.P.Th.M.M.), Department of Vascular Surgery (G.J.d.B.), and Department of Cardiology (H.M.N.), University Medical Center Utrecht, Utrecht, The Netherlands
| | - Willem P Th M Mali
- From the Julius Center for Health Sciences and Primary Care (E.J.E.H., Y.v.d.G., Y.T.v.d.S., J.W.B.), Department of Vascular Medicine (J.W.), Department of Radiology (P.A.d.J., W.P.Th.M.M.), Department of Vascular Surgery (G.J.d.B.), and Department of Cardiology (H.M.N.), University Medical Center Utrecht, Utrecht, The Netherlands
| | - Yolanda van der Graaf
- From the Julius Center for Health Sciences and Primary Care (E.J.E.H., Y.v.d.G., Y.T.v.d.S., J.W.B.), Department of Vascular Medicine (J.W.), Department of Radiology (P.A.d.J., W.P.Th.M.M.), Department of Vascular Surgery (G.J.d.B.), and Department of Cardiology (H.M.N.), University Medical Center Utrecht, Utrecht, The Netherlands
| | - Yvonne T van der Schouw
- From the Julius Center for Health Sciences and Primary Care (E.J.E.H., Y.v.d.G., Y.T.v.d.S., J.W.B.), Department of Vascular Medicine (J.W.), Department of Radiology (P.A.d.J., W.P.Th.M.M.), Department of Vascular Surgery (G.J.d.B.), and Department of Cardiology (H.M.N.), University Medical Center Utrecht, Utrecht, The Netherlands
| | - Joline W Beulens
- From the Julius Center for Health Sciences and Primary Care (E.J.E.H., Y.v.d.G., Y.T.v.d.S., J.W.B.), Department of Vascular Medicine (J.W.), Department of Radiology (P.A.d.J., W.P.Th.M.M.), Department of Vascular Surgery (G.J.d.B.), and Department of Cardiology (H.M.N.), University Medical Center Utrecht, Utrecht, The Netherlands
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Yoshioka K, Otani H, Shimazu T, Fujita M, Iwasaka T, Shiojima I. Sepiapterin prevents left ventricular hypertrophy and dilatory remodeling induced by pressure overload in rats. Am J Physiol Heart Circ Physiol 2015; 309:H1782-91. [PMID: 26408540 DOI: 10.1152/ajpheart.00417.2015] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Accepted: 09/22/2015] [Indexed: 01/01/2023]
Abstract
Uncoupling of nitric oxide (NO) synthase (NOS) has been implicated in left ventricular (LV) hypertrophy (LVH) and dilatory remodeling induced by pressure overload. We investigated whether administration of sepiapterin, a substrate of the salvage pathway of tetrahydrobiopterin synthesis, prevents LVH and dilatory LV remodeling by inhibiting NOS uncoupling and increasing bioavailable NO. Pressure overload was induced in rats by transverse aortic constriction (TAC). Concentric LVH developed during 8 wk after TAC, and dilatory LV remodeling and dysfunction developed between 8 and 16 wk after TAC associated with a decrease in capillary density. Oral administration of sepiapterin or the superoxide/peroxynitrite scavenger N-(2-mercaptopropionyl)-glycine for 8 wk after TAC inhibited oxidative stress, but only sepiapterin increased bioavailable NO and inhibited cardiomyocyte hypertrophy associated with a further increase in capillary density. When sepiapterin was administered between 8 and 16 wk after TAC, cardiomyocyte hypertrophy was regressed and capillary density was restored. This was associated with the inhibition of interstitial fibrosis and dilatory LV remodeling. N-nitro-l-arginine methyl ester abrogated all the beneficial effects of sepiapterin in rats with TAC. These results suggest that sepiapterin prevents concentric LVH and dilatory remodeling after TAC primarily by increasing the bioavailability of NO.
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MESH Headings
- Animals
- Aorta/surgery
- Biopterins/analogs & derivatives
- Biopterins/biosynthesis
- Capillaries/pathology
- Cell Size
- Constriction
- Dilatation, Pathologic/diagnostic imaging
- Dilatation, Pathologic/metabolism
- Enzyme Inhibitors/pharmacology
- Glycine/analogs & derivatives
- Glycine/pharmacology
- Heart/drug effects
- Hypertrophy, Left Ventricular/diagnostic imaging
- Hypertrophy, Left Ventricular/metabolism
- Hypertrophy, Left Ventricular/pathology
- Male
- Myocardium/metabolism
- Myocardium/pathology
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/pathology
- NG-Nitroarginine Methyl Ester/pharmacology
- Nitric Oxide/metabolism
- Nitric Oxide Synthase/drug effects
- Nitric Oxide Synthase/metabolism
- Organ Size
- Oxidative Stress/drug effects
- Pressure
- Pterins/pharmacology
- Rats
- Rats, Sprague-Dawley
- Sulfhydryl Compounds/pharmacology
- Ultrasonography
- Ventricular Dysfunction, Left/diagnostic imaging
- Ventricular Dysfunction, Left/metabolism
- Ventricular Dysfunction, Left/pathology
- Ventricular Remodeling/drug effects
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Affiliation(s)
- Kei Yoshioka
- Department of Internal Medicine II, Kansai Medical University, Moriguchi City, Japan
| | - Hajime Otani
- Department of Internal Medicine II, Kansai Medical University, Moriguchi City, Japan
| | - Takayuki Shimazu
- Department of Internal Medicine II, Kansai Medical University, Moriguchi City, Japan
| | - Masanori Fujita
- Department of Internal Medicine II, Kansai Medical University, Moriguchi City, Japan
| | - Toshiji Iwasaka
- Department of Internal Medicine II, Kansai Medical University, Moriguchi City, Japan
| | - Ichiro Shiojima
- Department of Internal Medicine II, Kansai Medical University, Moriguchi City, Japan
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Kontaraki JE, Marketou ME, Parthenakis FI, Maragkoudakis S, Zacharis EA, Petousis S, Kochiadakis GE, Vardas PE. Hypertrophic and antihypertrophic microRNA levels in peripheral blood mononuclear cells and their relationship to left ventricular hypertrophy in patients with essential hypertension. ACTA ACUST UNITED AC 2015; 9:802-810. [PMID: 26358152 DOI: 10.1016/j.jash.2015.07.013] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Revised: 07/03/2015] [Accepted: 07/23/2015] [Indexed: 12/22/2022]
Abstract
MicroRNAs regulate several aspects of physiological and pathologic cardiac hypertrophy, and they represent promising therapeutic targets in cardiovascular disease. We assessed the expression levels of the microRNAs miR-1, miR-133a, miR-26b, miR-208b, miR-499, and miR-21, in 102 patients with essential hypertension and 30 healthy individuals. All patients underwent two-dimensional echocardiography. MicroRNA expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly lower miR-133a (5.06 ± 0.50 vs. 13.20 ± 2.15, P < .001) and miR-26b (6.76 ± 0.53 vs. 9.36 ± 1.40, P = .037) and higher miR-1 (25.99 ± 3.07 vs. 12.28 ± 2.06, P = .019), miR-208b (22.29 ± 2.96 vs. 8.73 ± 1.59, P = .016), miR-499 (10.06 ± 1.05 vs. 5.70 ± 0.91, P = .033), and miR-21 (2.75 ± 0.15 vs. 1.82 ± 0.20, P = .002) expression levels compared with healthy controls. In hypertensive patients, we observed significant negative correlations of miR-1 (r = -0.374, P < .001) and miR-133a (r = -0.431, P < .001) and significant positive correlations of miR-26b (r = 0.302, P = .002), miR-208b (r = 0.426, P < .001), miR-499 (r = 0.433, P < .001) and miR-21 (r = 0.498, P < .001) expression levels with left ventricular mass index. Our data reveal that miR-1, miR-133a, miR-26b, miR-208b, miR-499, and miR-21 show distinct expression profiles in hypertensive patients relative to healthy individuals and they are associated with clinical indices of left ventricular hypertrophy in hypertensive patients. Thus, they may be related to heart hypertrophy in hypertensive patients and are possibly candidate therapeutic targets in hypertensive heart disease.
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Affiliation(s)
- Joanna E Kontaraki
- Molecular Cardiology Laboratory, Department of Cardiology, School of Medicine, University of Crete, Heraklion, Greece.
| | - Maria E Marketou
- Department of Cardiology, Heraklion University Hospital, Crete, Greece
| | | | | | | | - Stelios Petousis
- Department of Cardiology, Heraklion University Hospital, Crete, Greece
| | | | - Panos E Vardas
- Department of Cardiology, Heraklion University Hospital, Crete, Greece
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25
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Ying Z, Xie X, Bai Y, Chen M, Wang X, Zhang X, Morishita M, Sun Q, Rajagopalan S. Exposure to concentrated ambient particulate matter induces reversible increase of heart weight in spontaneously hypertensive rats. Part Fibre Toxicol 2015; 12:15. [PMID: 26108756 PMCID: PMC4479240 DOI: 10.1186/s12989-015-0092-6] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2015] [Accepted: 06/15/2015] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Exposure to ambient PM2.5 increases cardiovascular mortality and morbidity. To delineate the underlying biological mechanism, we investigated the time dependence of cardiovascular response to chronic exposure to concentrated ambient PM2.5 (CAP). METHODS Spontaneously hypertensive rats (SHR) were exposed to CAP for 15 weeks, and blood pressure (BP), cardiac function and structure, and inflammations of lung, hypothalamus, and heart were measured at different time points. RESULTS Chronic exposure to CAP significantly increased BP, and withdrawal from CAP exposure restored BP. Consistent with its BP effect, chronic exposure to CAP significantly decreased cardiac stroke volume and output in SHR, accompanied by increased heart weight and increased cardiac expression of hypertrophic markers ACTA1 and MYH7. Withdrawal from CAP exposure restored cardiac function, weight, and expression of hypertrophic markers, supporting the notion that cardiac dysfunction and hypertrophy is subsequent to hypertension. In agreement with the role of systemic inflammation in mediating the cardiovascular effects of CAP exposure, chronic exposure to CAP markedly increased expression of pro-inflammatory cytokines in lung, heart, and hypothalamus. However, withdrawal from exposure resolves inflammation in the heart and hypothalamus, but not in the lung, suggesting that CAP exposure-induced systemic inflammation may be independent of pulmonary inflammation. CONCLUSION Chronic exposure to CAP induces reversible cardiac dysfunction and hypertrophy, which is likely to be subsequent to the elevation in BP and induction of systemic inflammation as evidenced by increased mRNA expression of pro-inflammatory cytokines in diverse tissues.
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Affiliation(s)
- Zhekang Ying
- Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China. .,Department of Medicine Cardiology Division, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD, 21201, USA.
| | - Xiaoyun Xie
- Division of Geriatric Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, People's Republic of China.
| | - Yuntao Bai
- Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH, USA.
| | - Minjie Chen
- Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China. .,Department of Medicine Cardiology Division, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD, 21201, USA.
| | - Xiaoke Wang
- Department of Medicine Cardiology Division, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD, 21201, USA.
| | - Xuan Zhang
- Department of Medicine Cardiology Division, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD, 21201, USA.
| | - Masako Morishita
- Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA.
| | - Qinghua Sun
- Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH, USA.
| | - Sanjay Rajagopalan
- Department of Medicine Cardiology Division, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD, 21201, USA.
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26
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Nolly MB, Pinilla AO, Ennis IL, Cingolani HE, Morgan PE. Cardiac hypertrophy reduction in SHR by specific silencing of myocardial Na+/H+ exchanger. J Appl Physiol (1985) 2015; 118:1154-60. [DOI: 10.1152/japplphysiol.00996.2014] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Accepted: 02/26/2015] [Indexed: 12/13/2022] Open
Abstract
We examined the effect of specific and local silencing of sodium/hydrogen exchanger isoform 1 (NHE1) with a small hairpin RNA delivered by lentivirus (L-shNHE1) in the cardiac left ventricle (LV) wall of spontaneously hypertensive rats, to reduce cardiac hypertrophy. Thirty days after the lentivirus was injected, NHE1 protein expression was reduced 53.3 ± 3% in the LV of the L-shNHE1 compared with the control group injected with L-shSCR (NHE1 scrambled sequence), without affecting its expression in other organs, such as liver and lung. Hypertrophic parameters as LV weight-to-body weight and LV weight-to-tibia length ratio were significantly reduced in animals injected with L-shNHE1 (2.32 ± 0.5 and 19.30 ± 0.42 mg/mm, respectively) compared with L-shSCR-injected rats (2.68 ± 0.06 and 21.53 ± 0.64 mg/mm, respectively). Histochemical analysis demonstrated a reduction of cardiomyocytes cross-sectional area in animals treated with L-shNHE1 compared with L-shSCR (309,81 ± 20,86 vs. 424,52 ± 21 μm2, P < 0.05). Echocardiography at the beginning and at the end of the treatment showed that shNHE1 expression for 30 days induced 9% reduction of LV mass. Also, animals treated with L-shNHE1 exhibited a reduced LV wall thickness without changing LV diastolic dimension and arterial pressure, indicating an increased parietal stress. In addition, midwall shortening was not modified, despite the increased wall tension, suggesting an improvement of cardiac function. Chronic shNHE1 expression in the heart emerges as a possible methodology to reduce pathological cardiac hypertrophy, avoiding potentially undesired effects caused from a body-wide inhibition of NHE1.
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Affiliation(s)
- Mariela B. Nolly
- Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina
| | - Andrés O. Pinilla
- Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina
| | - Irene L. Ennis
- Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina
| | - Horacio E. Cingolani
- Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina
| | - Patricio E. Morgan
- Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina
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27
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Targeting γ-secretases protect against angiotensin II-induced cardiac hypertrophy. J Hypertens 2015; 33:843-50; discussion 850. [DOI: 10.1097/hjh.0000000000000463] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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28
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Wykrętowicz M, Katulska K, Milewska A, Krauze T. Left ventricular mass: correlation with fatness, hemodynamics and renal morphology. Pol J Radiol 2014; 79:426-30. [PMID: 25436020 PMCID: PMC4245148 DOI: 10.12659/pjr.891166] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Accepted: 06/15/2014] [Indexed: 11/16/2022] Open
Abstract
Background Left ventricular mass (LVM) is correlated with body composition and central hemodynamics as well as kidney function. Recently, fat-free mass has been considered to be more strongly correlated with LVM in comparison to other descriptors of fatness. We therefore address the question of whether comprehensive descriptors of fatness, central hemodynamics and renal characteristics demonstrate the association with left ventricular mass in healthy non-obese population. Material/Methods 119 healthy non-obese subjects (53 females, 66 males, mean age 50 yrs) were evaluated. Central hemodynamics was measured by Pulse Wave Analysis, left ventricular mass was assessed by echocardiography, fatness was evaluated by anthropometry, bioimpedance, and ultrasound. Results Left ventricular mass index (LVMI) correlated to the same extent with central and peripheral blood pressure but not with descriptors of wave reflection. Fat-free mass as well as intraabdominal fat correlated to a similar extent with LVMI. Kidney morphological characteristics indexed to body surface area were associated inversely and independently with LVMI. Conclusions Comprehensive assessment of fatness reinforced the concept that intraabdominal fat compartment is strongly correlated with left ventricular mass. Descriptors of wave reflection are not associated with left ventricular mass. The interrelationsh between kidney morphology and LVMI indicates that such associations may be a biologically plausible phenomenon.
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Affiliation(s)
| | | | - Agata Milewska
- Department of Cardiology - Intensive Therapy, University School of Medicine, Poznań, Poland
| | - Tomasz Krauze
- Department of Cardiology - Intensive Therapy, University School of Medicine, Poznań, Poland
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29
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Abstract
Hypertension is a powerful risk factor for cardiovascular mortality and morbidity, including heart failure with both preserved and reduced ejection fraction. Hypertensive heart disease (HHD) defines the complex and diverse perturbations of cardiac structure and function occurring secondary to hypertension. Left ventricular hypertrophy (LVH) is one of the most recognized features of HHD and is an established risk factor for adverse cardiovascular (CV) outcomes in hypertension. Beyond LVH, LV geometry provides additional information regarding the cardiac response to hypertension. Imaging studies from larger cohorts of hypertensive patients reveal wide variability in the prevalence of LVH and LV geometric patterns, with the prevalence of concentric LVH similar to that of eccentric LVH. Hypertension is also associated with concomitant impairments in LV diastolic and systolic function. It remains uncertain why patients develop different patterns of LVH, although demographics and clinical comorbidities appear to influence that response.
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Affiliation(s)
- Mário Santos
- Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, Porto, Portugal
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30
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Solomon SD. Diagnostic evaluation: target organ damage: cardiac. JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION : JASH 2014; 8:848-850. [PMID: 25455010 DOI: 10.1016/j.jash.2014.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
MESH Headings
- Age Distribution
- Aged
- Aged, 80 and over
- Echocardiography, Doppler/methods
- Electrocardiography/methods
- Female
- Follow-Up Studies
- Heart Failure, Diastolic/diagnosis
- Heart Failure, Diastolic/epidemiology
- Heart Failure, Diastolic/etiology
- Humans
- Hypertension/complications
- Hypertension/diagnosis
- Hypertension/drug therapy
- Hypertrophy, Left Ventricular/diagnosis
- Hypertrophy, Left Ventricular/epidemiology
- Hypertrophy, Left Ventricular/etiology
- Incidence
- Magnetic Resonance Imaging, Cine/methods
- Male
- Middle Aged
- Practice Guidelines as Topic
- Risk Assessment
- Severity of Illness Index
- Sex Distribution
- Societies, Medical
- Survival Analysis
- Time Factors
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31
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Yilmaz H, Gurel OM, Celik HT, Bozkurt A, Yildirim ME, Bilgic I, Bilgic MA, Bavbek N, Akcay A. Relationship of galectin-3 to left ventricular geometry and hypertrophy in chronic hemodialysis patients. Herz 2014; 40:702-8. [PMID: 24924396 DOI: 10.1007/s00059-014-4111-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Revised: 04/15/2014] [Accepted: 04/24/2014] [Indexed: 12/29/2022]
Abstract
AIM AND BACKGROUND Galectin-3 (Gal-3) is used to determine the prognosis of heart failure. Some studies revealed that Gal-3 promoted cardiac hypertrophy but there is no study in which the relationship between Gal-3 and left ventricular hypertrophy (LVH) geometry in patients without diastolic and systolic function impairment has been explored. The aim of the study was to analyze associations between plasma Gal-3 levels, LVH, and LV geometry in maintenance hemodialysis (HD) patients without systolic and diastolic dysfunction. PATIENTS AND METHODS The study group included 105 patients (53 women and 52 men)--with an average age of 58.2 ± 12.6 years, treated with HD for an average of 45 ± 32 months--and 60 healthy controls. The Gal-3 and other biochemical parameters were measured and color Doppler echocardiography was performed. For this study LVH was considered present when the LV mass index (LVMI) exceeded 95 g/m(2) in women and 115 g/m(2) in men. Left ventricular geometry was classified into the four groups on the basis of left ventricular mass and relative wall thickness (RWT). RESULTS Concentric hypertrophy (CH, 40.9 %, n = 43) was the commonest geometric pattern in our study. The Gal-3 levels in CH patients were not different from the patients with eccentric hypertrophy (EH). Plasma levels of Gal-3 correlated with LVMI (r = 0.617, p < 0.001), parathyroid hormone (PTH, r = 0.408, p < 0.001), uric acid (r = 0.281, p = 0.004), C-reactive protein (CRP, r = 0.412, p < 0.001), and RWT (r = 0.281, p = 0.004) but were inversely correlated with albumin (r = - 0.466, P < 0.001) in the whole group. Plasma levels of Gal-3 were associated with LVMI (r = 0.812, P < 0.001), RWT (r = 0.318, p = 0.001), and CRP(r = 0.381, p < 0.001) in maintenance hemodialysis patients. CONCLUSION The Gal-3 level is related to left ventricular hypertrophy and it is independent of left ventricle geometry. The relationship between LVH and Gal-3 might be direct or it may also be inflammation-related.
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Affiliation(s)
- H Yilmaz
- Department of Internal Medicine, Section of Nephrology, Turgut Ozal University, School of Medicine, Alparslan Türkes Cad. No: 57, 06510, Emek/Ankara, Turkey,
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32
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33
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34
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Kontaraki JE, Marketou ME, Zacharis EA, Parthenakis FI, Vardas PE. MicroRNA-9 and microRNA-126 expression levels in patients with essential hypertension: potential markers of target-organ damage. ACTA ACUST UNITED AC 2014; 8:368-75. [PMID: 24794206 DOI: 10.1016/j.jash.2014.03.324] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 03/21/2014] [Accepted: 03/21/2014] [Indexed: 12/21/2022]
Abstract
MicroRNAs (miRs), as essential gene expression regulators, modulate cardiovascular development and disease and thus they are emerging as potential biomarkers and therapeutic targets in cardiovascular disease, including hypertension. We assessed the expression levels of the microRNAs miR-9 and miR-126 in 60 patients with untreated essential hypertension and 29 healthy individuals. All patients underwent two-dimensional echocardiography and 24-hour ambulatory blood pressure monitoring. MicroRNA expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly lower miR-9 (9.69 ± 1.56 vs 41.08 ± 6.06; P < .001) and miR-126 (3.88 ± 0.47 vs 8.96 ± 1.69; P < .001) expression levels compared with healthy controls. In hypertensive patients, miR-9 expression levels showed a significant positive correlation (r = 0.437; P < .001) with left ventricular mass index. Furthermore, both miR-9 (r = 0.312; P = .015) and miR-126 (r = 0.441; P < .001) expression levels in hypertensive patients showed significant positive correlations with the 24-hour mean pulse pressure. Our data reveal that miR-9 and miR-126 are closely related to essential hypertension in humans, as they show a distinct expression profile in hypertensive patients relative to healthy individuals, and they are associated with clinical prognostic indices of hypertensive target-organ damage in hypertensive patients. Thus, they may possibly represent potential biomarkers and candidate therapeutic targets in essential hypertension.
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Affiliation(s)
- Joanna E Kontaraki
- Molecular Cardiology Laboratory, School of Medicine, University of Crete, Greece.
| | - Maria E Marketou
- Department of Cardiology, Heraklion University Hospital, Crete, Greece
| | | | | | - Panos E Vardas
- Department of Cardiology, Heraklion University Hospital, Crete, Greece
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35
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Right ventricular hypertrophy in systemic hypertension: an updated review of clinical studies. J Hypertens 2013; 31:858-65. [PMID: 23449015 DOI: 10.1097/hjh.0b013e32835f17e5] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
AIM Experimental and clinical evidence supports the view that right ventricular hypertrophy (RVH) may parallel left ventricular hypertrophy in systemic hypertension; a comprehensive analysis of this issue, however, is lacking. Thus, we analyzed the literature in order to provide an updated information on the right ventricular structural changes associated to systemic hypertension. DESIGN A literature search using the key words 'right ventricle' 'right ventricular hypertrophy', 'biventricular hypertrophy' 'right and left ventricular hypertrophy'. 'hypertension', 'echocardiography' was performed in order to identify relevant articles. Full articles published in English language in the last three decades reporting studies in adult hypertensive individuals were considered. RESULTS A total of 13 studies, including 1290 untreated (45%) and treated hypertensive patients and 259 normotensive controls, were considered. Overall, in hypertensive individuals right ventricular wall was thicker than in normotensive counterparts (standardized difference 1.3 mm, P < 0.001). RVH prevalence consistently varied among studies (17.0-80.0%) with an average of 28.6% in the pooled population. This was also the case for LVH prevalence rates (9.0-100%) with an average value of 30.6%. CONCLUSION Clinical studies consistently indicate that RVH is a common cardiac phenotype in systemic hypertension. As this finding is based on a limited number of cross-sectional studies including small population samples, further investigations are needed to determine the clinical utility and prognostic value of this phenotype in clinical practice.
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36
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Association of cardiotrophin-1 with left ventricular systolic properties in asymptomatic hypertensive patients. J Hypertens 2013; 31:587-94. [PMID: 23429662 DOI: 10.1097/hjh.0b013e32835ca903] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
OBJECTIVES Cardiotrophin-1 (CT-1) induces hypertrophic growth and contractile dysfunction in cardiomyocytes. This cross-sectional study was aimed to analyze CT-1 associations with echocardiographically assessed left ventricular systolic properties taking into account the influence of left ventricular growth [i.e. left ventricular hypertrophy (LVH) and inappropriate left ventricular mass (iLVM)] in asymptomatic hypertensive patients. METHODS Serum CT-1 was measured by ELISA in 278 asymptomatic hypertensive patients with a left ventricular ejection fraction more than 50% and in 25 age and sex-matched normotensive patients. RESULTS Serum CT-1 was increased in hypertensive patients as compared to normotensive patients. CT-1 was directly correlated with parameters of left ventricular mass (LVM) and inversely correlated with parameters assessing myocardial systolic function and left ventricular chamber contractility in hypertensive patients, these associations being independent of a number of potential confounding factors. Interestingly, the associations of CT-1 with myocardial systolic function were independent of LVM even in patients with LVH or iLVM. In addition, there was a significant increment of serum CT-1 in hypertensive patients with LVH or iLVM, especially in those in whom LVH or iLVM were accompanied by impaired myocardial systolic function, as compared to the remaining hypertensive patients and normotensive patients. Plasma amino-terminal pro-brain natriuretic peptide was not correlated with any of the assessed left ventricular systolic parameters in either group of patients. CONCLUSION These findings suggest that serum CT-1 is associated with myocardial systolic dysfunction in asymptomatic hypertensive patients, independently of LVM, even in those patients with pathologic left ventricular growth.
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37
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Dominguez-Rodriguez A, Arroyo-Ucar E, Abreu-Gonzalez P, Tome MCP, Hernandez-Garcia C, del Carmen García-Baute M, Avanzas P. Cardiopulmonary exercise testing and prognostic assessment of hypertensive cardiomyopathy: An emerging application. Int J Cardiol 2013. [DOI: 10.1016/j.ijcard.2012.11.108] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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38
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Rabkin SW. Differences in coronary blood flow in aortic regurgitation and systemic arterial hypertension have implications for diastolic blood pressure targets: a systematic review and meta-analysis. Clin Cardiol 2013; 36:728-36. [PMID: 24037941 DOI: 10.1002/clc.22194] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Accepted: 07/09/2013] [Indexed: 11/06/2022] Open
Abstract
The objective was to evaluate coronary blood flow (CBF) in patients with systemic arterial hypertension (HTN) and to compare it with CBF in patients with aortic regurgitation (AR). A systematic literature search was conducted using the reference terms "coronary blood flow" and either "aortic regurgitation" or "hypertension." The selection criteria included CBF measurement in a concomitant control group, except studies evaluating CBF with aortic-valve replacement surgery. Twenty-two studies met the inclusion criteria. There were 318 persons with HTN, with 185 controls; and 102 persons with AR, with 144 controls. Despite an overall increase in CBF in HTN, CBF per gram of left ventricular mass was significantly (P < 0.0001) reduced. In contrast, CBF per gram of left ventricular mass was significantly (P = 0.004) increased in AR. Aortic regurgitation was associated with a significant (P < 0.0001) increase in CBF during systole and away from diastole, in contrast to persons with HTN. Aortic-valve replacement reversed the increase in systolic CBF. These data suggest that patients with HTN are more vulnerable than patients with AR to lower diastolic blood pressure (DBP), because resting CBF is compromised in HTN. Furthermore, patients with HTN may not compensate for DBP reductions by shifting CBF to systole, such as can occur with the low DBP in AR. Lower DBP in patients with AR cannot be used to justify treating patients with HTN to similar DBP because of the dramatic differences in CBF between the 2 conditions.
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Affiliation(s)
- Simon W Rabkin
- Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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39
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Cuspidi C, Negri F, Tadic MV, Sala C, Parati G. Left atrial enlargement and right ventricular hypertrophy in essential hypertension. Blood Press 2013; 23:89-95. [PMID: 23763624 DOI: 10.3109/08037051.2013.803312] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
AIM Diastolic dysfunction related to hypertensive left ventricular hypertrophy (LVH) has been shown to affect right-sided cardiac morphology and haemodynamics. As left atrial enlargement (LAE) is a marker of chronically elevated left ventricular (LV) filling pressure and diastolic dysfunction, we investigated the relationship between LAE and right ventricular hypertrophy (RVH) in systemic hypertension. METHODS A total of 330 essential hypertensives, categorized according to tertiles of left atrial (LA) diameter indexed to body surface area were considered for the analysis. All subjects underwent a quantitative echocardiographic examination as well as extensive clinical and laboratory investigations. RVH was defined as anterior right ventricular (RV) wall thickness ≥ 6.0/5.5 mm in men and women, respectively, and LVH as LV mass index ≥ 51/47 g/m(2.7) in men and women, respectively. RESULTS The prevalence of LVH increased across LA diameter tertiles from 21.0% to 50% and that of RVH from 26.3% to 41.8% (p < 0.01for both). This was also the case for biventricular hypertrophy (from 10.0% to 26.0%, p < 0.01). Differences in both LV and RV structure across LA diameter tertiles remained significant after adjusting for age, office systolic/diastolic blood pressure and duration of hypertension. Similar results were obtained when study population was divided according to absolute LA diameter tertiles. CONCLUSIONS Our findings provide further evidence of an interaction between left and right chambers in systemic hypertension by showing that LAE is associated with RVH. The clinical and prognostic implications of such observation remain be evaluated in future prospective studies.
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Affiliation(s)
- Cesare Cuspidi
- Department of Health Science, University of Milano-Bicocca , Milano , Italy
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40
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Díez J. Hypertensive heart disease. Hypertension 2013. [DOI: 10.2217/ebo.12.497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- Javier Díez
- Javier Díez is Full Professor of Medicine at the University of Navarra (Pamplona, Spain). His group studies the mechanisms involved in myocardial remodeling associated with cardiac pressure overload, as well as noninvasive biomarkers and novel therapeutic targets for myocardial remodeling
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Boonpeng H, Yusoff K. The utility of copy number variation (CNV) in studies of hypertension-related left ventricular hypertrophy (LVH): rationale, potential and challenges. Mol Cytogenet 2013; 6:8. [PMID: 23448375 PMCID: PMC3599593 DOI: 10.1186/1755-8166-6-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2012] [Accepted: 01/03/2013] [Indexed: 01/08/2023] Open
Abstract
The ultimate goal of human genetics is to understand the role of genome variation in elucidating human traits and diseases. Besides single nucleotide polymorphism (SNP), copy number variation (CNV), defined as gains or losses of a DNA segment larger than 1 kb, has recently emerged as an important tool in understanding heritable source of human genomic differences. It has been shown to contribute to genetic susceptibility of various common and complex diseases. Despite a handful of publications, its role in cardiovascular diseases remains largely unknown. Here, we deliberate on the currently available technologies for CNV detection. The possible utility and the potential roles of CNV in exploring the mechanisms of cardiac remodeling in hypertension will also be addressed. Finally, we discuss the challenges for investigations of CNV in cardiovascular diseases and its possible implications in diagnosis of hypertension-related left ventricular hypertrophy (LVH).
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Affiliation(s)
- Hoh Boonpeng
- Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai, Buloh, 47000, Malaysia.
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Whelton PK, Appel LJ, Sacco RL, Anderson CAM, Antman EM, Campbell N, Dunbar SB, Frohlich ED, Hall JE, Jessup M, Labarthe DR, MacGregor GA, Sacks FM, Stamler J, Vafiadis DK, Van Horn LV. Sodium, blood pressure, and cardiovascular disease: further evidence supporting the American Heart Association sodium reduction recommendations. Circulation 2012; 126:2880-9. [PMID: 23124030 DOI: 10.1161/cir.0b013e318279acbf] [Citation(s) in RCA: 320] [Impact Index Per Article: 24.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Recent reports of selected observational studies and a meta-analysis have stirred controversy and have become the impetus for calls to abandon recommendations for reduced sodium intake by the US general population. A detailed review of these studies documents substantial methodological concerns that limit the usefulness of these studies in setting, much less reversing, dietary recommendations. Indeed, the evidence base supporting recommendations for reduced sodium intake in the general population remains robust and persuasive. The American Heart Association is committed to improving the health of all Americans through implementation of national goals for health promotion and disease prevention, including its recommendation to reduce dietary sodium intake to <1500 mg/d.
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Fallo F, Catena C, Camozzi V, Luisetto G, Cosma C, Plebani M, Lupia M, Tona F, Sechi LA. Low serum 25-hydroxyvitamin D levels are associated with left ventricular hypertrophy in essential hypertension. Nutr Metab Cardiovasc Dis 2012; 22:871-876. [PMID: 21937207 DOI: 10.1016/j.numecd.2011.06.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2011] [Revised: 06/15/2011] [Accepted: 06/20/2011] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIM Low serum 25-hydroxyvitamin D [25(OH)D] levels may have an important role in predisposing to hypertension and myocardial disease. We investigated the relationship between 25(OH)D and left ventricular (LV) structure and function, assessed by echocardiography, in a series of patients with essential hypertension (EH). METHODS AND RESULTS Sixty-two newly diagnosed never-treated patients (32 male/30 female), aged 18-65 years, with grade 1-2 hypertension, no diabetes, no obesity, no hyperlipidemia, and no cardiopulmonary, renal, or hepatic disease, were studied. Twenty-four healthy normotensive sex-, age-, BMI-matched subjects served as controls. Hypertensive patients with 25(OH)D deficiency, defined as serum 25(OH)D levels <50 nmol/L, had higher prevalence of LV hypertrophy (LVH) than their 25(OH)D-sufficient counterparts (57.1 vs 17.6%, P = 0.02); no differences between the two groups were found in blood pressure levels as well as in other biochemical and hormone parameters. There was an inverse correlation between LV mass index and 25(OH)D levels (r = -0.366, P < 0.003) and a direct correlation between LV mass index and BMI (r = 0.333, P < 0.006) in the entire hypertensive population. The two variables remained independently associated with LVH at multivariable logistic regression analysis (OR 1.05, P < 0.005 and OR 1.25, P = 0.03, respectively). Prevalence of 25(OH)D deficiency was similar in EH patients and controls (45.1 vs 41.6%, P = 0.89), whereas no correlation between echocardiographic parameters and hormone levels was found. CONCLUSIONS In the absence of major cardiovascular risk factors, 25(OH)D deficiency is a frequent finding in EH patients and is independently associated with LVH.
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Affiliation(s)
- F Fallo
- Clinica Medica 3, Department of Medical and Surgical Sciences, University of Padova, Via Ospedale 105, 35128 Padova, Italy.
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Mukaddam-Daher S. An “I” on Cardiac Hypertrophic Remodelling: Imidazoline Receptors and Heart Disease. Can J Cardiol 2012; 28:590-598. [DOI: 10.1016/j.cjca.2012.02.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2012] [Revised: 02/01/2012] [Accepted: 02/14/2012] [Indexed: 11/24/2022] Open
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Negri F, Sala C, Re A, Mancia G, Cuspidi C. Left ventricular geometry and diastolic function in the hypertensive heart: impact of age. Blood Press 2012; 22:1-8. [PMID: 22853636 DOI: 10.3109/08037051.2012.707307] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND AND AIM The impact of aging on the relationship between left ventricular (LV) mass/geometry and diastolic function as assessed by updated echocardiographic methods, such as tissue Doppler, is poorly defined. We investigated this issue in a cohort of hypertensive patients. METHODS A total of 660 hypertensives (mean age 65 ± 13 years, 48% men) with preserved LV systolic function underwent a comprehensive echo-Doppler examination for routine clinical indications. For the present analysis, the subjects have been divided in two age groups (<65 or ≥65 years). RESULTS Overall, 61% of subjects fulfilled the criteria for LVH, 18% for left atrial (LA) enlargement and 11% for altered LV filling index. Concentric LV geometry was 1.4-fold higher in older hypertensives than in younger counterparts; also the prevalence of LA enlargement and altered LV filling was 2.0- and 1.9-fold higher in the former group, respectively. In older hypertensives, at variance from younger ones, neither LV mass nor relative wall thickness (RWT), a continuous index of LV geometry, were independently correlated to conventional as well as tissue Doppler LV diastolic indexes. CONCLUSIONS Our findings suggest the relationship between cardiac hypertrophy and diastolic function in hypertensive subjects is affected by aging-associated factors unrelated to the amount of LV mass as assessed by standard echocardiography.
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Affiliation(s)
- Francesca Negri
- Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milano, Italy
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McCollum LT, Gallagher PE, Tallant EA. Angiotensin-(1-7) abrogates mitogen-stimulated proliferation of cardiac fibroblasts. Peptides 2012; 34:380-8. [PMID: 22326709 PMCID: PMC3326596 DOI: 10.1016/j.peptides.2012.01.020] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2011] [Revised: 01/24/2012] [Accepted: 01/24/2012] [Indexed: 12/16/2022]
Abstract
Previous studies showed that angiotensin-(1-7) [Ang-(1-7)] attenuates cardiac remodeling by reducing both interstitial and perivascular fibrosis. Although a high affinity binding site for Ang-(1-7) was identified on cardiac fibroblasts, the molecular mechanisms activated by the heptapeptide hormone were not identified. We isolated cardiac fibroblasts from neonatal rat hearts to investigate signaling pathways activated by Ang-(1-7) that participate in fibroblast proliferation. Ang-(1-7) reduced (3)H-thymidine, -leucine and -proline incorporation into cardiac fibroblasts stimulated with serum or the mitogen endothelin-1 (ET-1), demonstrating that the heptapeptide hormone decreases DNA, protein and collagen synthesis. The reduction in DNA synthesis by Ang-(1-7) was blocked by the AT((1-7)) receptor antagonist [d-Ala(7)]-Ang-(1-7), showing specificity of the response. Treatment of cardiac fibroblasts with Ang-(1-7) reduced the Ang II- or ET-1-stimulated increase in phospho-ERK1 and -ERK2. In contrast, Ang-(1-7) increased dual-specificity phosphatase DUSP1 immunoreactivity and mRNA, suggesting that the heptapeptide hormone increases DUSP1 to reduce MAP kinase phosphorylation and activity. Incubation of cardiac fibroblasts with ET-1 increased cyclooxygenase 2 (COX-2) and prostaglandin synthase (PGES) mRNAs, while Ang-(1-7) blocked the increase in both enzymes, suggesting that the heptapeptide hormone alters the concentration and the balance between the proliferative and anti-proliferative prostaglandins. Collectively, these results indicate that Ang-(1-7) participates in maintaining cardiac homeostasis by reducing proliferation and collagen production by cardiac fibroblasts in association with up-regulation of DUSP1 to reduce MAP kinase activities and attenuation of the synthesis of mitogenic prostaglandins. Increased Ang-(1-7) or agents that enhance production of the heptapeptide hormone may prevent abnormal fibrosis that occurs during cardiac pathologies.
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Affiliation(s)
- LaTronya T McCollum
- The Hypertension and Vascular Research Center, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1032, USA
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Abstract
This review discusses cardiac consequences of pressure overload. In response to elevated pressure, the ventricular hypertrophy compensates for the increased wall stress. However, the ventricular hypertrophy involves numerous structural adaptations that may lead to ventricular dysfunction and, eventually, heart failure. Particular emphasis is placed on molecular mechanisms that govern the development of hypertrophy and that may lead to maladaptive structural changes resulting in adverse cardiac events.
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Sgk1 sensitivity of Na(+)/H(+) exchanger activity and cardiac remodeling following pressure overload. Basic Res Cardiol 2012; 107:236. [PMID: 22212557 DOI: 10.1007/s00395-011-0236-2] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2011] [Revised: 11/15/2011] [Accepted: 12/04/2011] [Indexed: 01/08/2023]
Abstract
Sustained increase of cardiac workload is known to trigger cardiac remodeling with eventual development of cardiac failure. Compelling evidence points to a critical role of enhanced cardiac Na(+)/H(+) exchanger (NHE1) activity in the underlying pathophysiology. The signaling triggering up-regulation of NHE1 remained, however, ill defined. The present study explored the involvement of the serum- and glucocorticoid-inducible kinase Sgk1 in cardiac remodeling due to transverse aortic constriction (TAC). To this end, experiments were performed in gene targeted mice lacking functional Sgk1 (sgk1 (-/-)) and their wild-type controls (sgk1 (+/+)). Transcript levels have been determined by RT-PCR, cytosolic pH (pH( i )) utilizing 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, Na(+)/H(+) exchanger activity by the Na(+)-dependent realkalinization after an ammonium pulse, ejection fraction (%) utilizing cardiac cine magnetic resonance imaging and cardiac glucose uptake by PET imaging. As a result, TAC increased the mRNA expression of Sgk1 in sgk1 (+/+) mice, paralleled by an increase in Nhe1 transcript levels as well as Na(+)/H(+) exchanger activity, all effects virtually abrogated in sgk1 (-/-) mice. In sgk1 (+/+) mice, TAC induced a decrease in Pgc1a mRNA expression, while Spp1 mRNA expression was increased, both effects diminished in the sgk1 (-/-) mice. TAC was followed by a significant increase of heart and lung weight in sgk1 (+/+) mice, an effect significantly blunted in sgk1 (-/-) mice. TAC increased the transcript levels of Anp and Bnp, effects again significantly blunted in sgk1 (-/-) mice. TAC increased transcript levels of Collagen I and III as well as Ctgf mRNA and CTGF protein abundance, effects significantly blunted in sgk1 (-/-) mice. TAC further decreased the ejection fraction in sgk1 (+/+) mice, an effect again attenuated in sgk1 (-/-) mice. Also, cardiac FDG-glucose uptake was increased to a larger extent in sgk1 (+/+) mice than in sgk1 (-/-) mice after TAC. These observations point to an important role for SGK1 in cardiac remodeling and development of heart failure following an excessive work load.
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Prevalence of left-ventricular hypertrophy in hypertension: an updated review of echocardiographic studies. J Hum Hypertens 2011; 26:343-9. [PMID: 22113443 DOI: 10.1038/jhh.2011.104] [Citation(s) in RCA: 195] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Left-ventricular hypertrophy (LVH) is a cardinal manifestation of hypertensive organ damage associated with an increased cardiovascular (CV) risk. We reviewed recent literature on the prevalence of LVH, as assessed by echocardiography, in order to offer an updated information on the magnitude of subclinical alterations in LV structure in contemporary human hypertension. A MEDLINE search using key words 'left ventricular hypertrophy', 'hypertension', 'echocardiography' and 'cardiac organ damage' was performed in order to identify relevant papers. Full articles published in English language in the last decade, (1 January 2000-1 December 2010), reporting studies in adult or elderly individuals, were considered. A total of 30 studies, including 37,700 untreated and treated patients (80.3% Caucasian, 52.4% men, 9.6% diabetics, 2.6% with CV disease) were considered. LVH was defined by 23 criteria; its prevalence ranged from 36% (conservative criteria) to 41% (less conservative criteria) in the pooled population. LVH prevalence was not different between women and men (range 37.9-46.2 versus 36.0-43.5%, respectively). Eccentric LVH was more frequent than concentric hypertrophy (range 20.3-23.0 versus 14.8-15.8, respectively, P<0.05); concentric phenotype was found in a consistent fraction (20%) of both genders. Despite the improved management of hypertension in the last two decades, LVH remains a highly frequent biomarker of cardiac damage in the hypertensive population. Our analysis calls for a more aggressive treatment of hypertension and related CV risk factors leading to LVH.
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The LOX-1 3'UTR188CT polymorphism and coronary artery disease in Turkish patients. Mol Biol Rep 2011; 39:4351-8. [PMID: 21901421 DOI: 10.1007/s11033-011-1222-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2011] [Accepted: 08/29/2011] [Indexed: 10/17/2022]
Abstract
In coronary artery disease (CAD), a potentially reversible factor leading to cardiac death is left ventricular hypertrophy (LVH). The 3'untranslated region (3'UTR) 188CT polymorphism of lectin-like oxidized low-density lipoproteins receptor-1 (LOX-1) gene has been associated with an increased risk for CAD. We aim to investigate, in a Turkish population, whether 3'UTR188CT variation could affect the development of LVH in CAD patients. In a population-based case-control study, we compared 83 cases with CAD and 99 healthy controls for this polymorphism. The LOX-1 3'UTR188CT genotypes were determined by PCR-RFLP technique. LOX-1 3'UTR188 TT genotype was associated with significantly increased systolic blood pressure (P = 0.047) and risk of LVH (P = 0.014, OR: 3.541) when compared with the C allele carriers. In addition, the TT genotype was positively associated with decreased levels of HDL-cholesterol in the control subjects (P = 0.031) and increased levels of VLDL-C in the patient group (P = 0.009). The LOX-1 3'UTR188CT gene polymorphism may predispose to the development of LVH in CAD patients, dependent on blood pressure.
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