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Abdelnabi M, Almaghraby A, Benjanuwattra J, Saleh Y, Ghazi R, Azeem AAE. The usefulness of initial serum ferritin level as a predictor of in-hospital mortality in STEMI. THE BRITISH JOURNAL OF CARDIOLOGY 2023; 30:20. [PMID: 39144088 PMCID: PMC11321463 DOI: 10.5837/bjc.2023.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2024]
Abstract
Several studies have shown that elevated serum ferritin level is associated with a higher risk of coronary artery disease. Recently, it has been shown that high serum ferritin levels in men are independently correlated with an increased risk of cardiovascular mortality. This study aimed to investigate the possible correlation between the initial serum ferritin level and in-hospital mortality in patients presenting with ST-elevation myocardial infarction (STEMI). This retrospective cohort study included 890 patients who presented with acute STEMI and underwent successful primary percutaneous coronary intervention (PPCI) according to the standard techniques during the period from 1 May 2020 to 1 May 2021. At the time of admission, an initial serum ferritin level was measured in all patients. Comparison between initial ferritin levels was made between two groups: died and survived. Propensity matching was performed to exclude confounding factors effect. Forty-one patients had in-hospital mortality. There was no significant difference between both groups regarding baseline clinical characteristics. Initial serum ferritin levels were higher in deceased patients, even after propensity matching. In conclusion, even after propensity matching, initial ferritin levels were significantly higher in patients who died after being admitted for STEMI.
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Affiliation(s)
| | | | - Juthipong Benjanuwattra
- Internal Medicine Resident Internal Medicine Department, Texas Tech University Health Sciences Center, 3601 4 Street, Lubbock, Texas 79430, USA
| | - Yehia Saleh
- Cardiology Fellow Cardiology Department, Houston Methodist Debakey Cardiology Associates, 6550 Fannin St tower 1901, Houston, Texas 77030, USA
| | | | - Ahmed Abd El Azeem
- Lecturer of Cardiology Cardiology Department, Faculty of Medicine, Alexandria University, Champollion Street, El-Khartoum Square, El Azareeta Medical Campus, Alexandria 21131, Egypt
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Martikos G, Kapelouzou A, Peroulis M, Paspala A, Athanasiadis D, Machairas A, Liakakos T, Moulakakis K, Vasdekis S, Lazaris AM. Remote Ischemic Preconditioning Decreases the Magnitude of Hepatic Ischemia-Reperfusion Injury on a Swine Model of Supraceliac Aortic Cross-Clamping. Ann Vasc Surg 2018; 48:241-250. [DOI: 10.1016/j.avsg.2017.08.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2017] [Revised: 08/11/2017] [Accepted: 08/18/2017] [Indexed: 12/15/2022]
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Vanella L, Barbagallo I, Tibullo D, Forte S, Zappalà A, Li Volti G. The non-canonical functions of the heme oxygenases. Oncotarget 2018; 7:69075-69086. [PMID: 27626166 PMCID: PMC5356613 DOI: 10.18632/oncotarget.11923] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Accepted: 09/05/2016] [Indexed: 11/25/2022] Open
Abstract
Heme oxygenase (HO) isoforms catalyze the conversion of heme to carbon monoxide (CO) and biliverdin with a concurrent release of iron, which can drive the synthesis of ferritin for iron sequestration. Most of the studies so far were directed at evaluating the protective effect of these enzymes because of their ability to generate antioxidant and antiapoptotic molecules such as CO and bilirubin. Recent evidences are suggesting that HO may possess other important physiological functions, which are not related to its enzymatic activity and for which we would like to introduce for the first time the term “non canonical functions”. Recent evidence suggest that both HO isoforms may form protein-protein interactions (i.e. cytochrome P450, adiponectin, CD91) thus serving as chaperone-like protein. In addition, truncated HO-1 isoform was localized in the nuclear compartment under certain experimental conditions (i.e. excitotoxicity, hypoxia) regulating the activity of important nuclear transcription factors (i.e. Nrf2) and DNA repair. In the present review, we discuss three potential signaling mechanisms that we refer to as the non-canonical functions of the HO isoforms: protein-protein interaction, intracellular compartmentalization, and extracellular secretion. The aim of the present review is to describe each of this mechanism and all the aspects warranting additional studies in order to unravel all the functions of the HO system.
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Affiliation(s)
- Luca Vanella
- Department of Drug Sciences, University of Catania, Catania, Italy
| | | | - Daniele Tibullo
- Division of Haematology, AOU "Policlinico - Vittorio Emanuele", University of Catania, Catania, Italy
| | - Stefano Forte
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.,Istituto Oncologico del Mediterraneo Ricerca srl Viagrande, Catania, Italy
| | - Agata Zappalà
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Giovanni Li Volti
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.,EuroMediterranean Institute of Science and Technology, Palermo, Italy
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Tissue heme oxygenase-1 exerts anti-inflammatory effects on LPS-induced pulmonary inflammation. Mucosal Immunol 2016; 9:98-111. [PMID: 25943274 DOI: 10.1038/mi.2015.39] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2014] [Accepted: 04/01/2015] [Indexed: 02/04/2023]
Abstract
Heme oxygenase-1 (HO-1) has been shown to display anti-inflammatory properties in models of acute pulmonary inflammation. For the first time, we investigated the role of leukocytic HO-1 using a model of HO-1(flox/flox) mice lacking leukocytic HO-1 that were subjected to lipopolysaccharide (LPS)-induced acute pulmonary inflammation. Immunohistology and flow cytometry demonstrated that activation of HO-1 using hemin decreased migration of polymorphonuclear leukocytes (PMNs) to the lung interstitium and bronchoalveolar lavage (BAL) in the wild-type and, surprisingly, also in HO-1(flox/flox) mice, emphasizing the anti-inflammatory potential of nonmyeloid HO-1. Nevertheless, hemin reduced the CXCL1, CXCL2/3, tumor necrosis factor-α (TNFα), and interleukin 6 (IL6) levels in both animal strains. Microvascular permeability was attenuated by hemin in wild-type and HO-1(flox/flox) mice, indicating a crucial role of non-myeloid HO-1 in endothelial integrity. The determination of the activity of HO-1 in mouse lungs revealed no compensatory increase in the HO-1(flox/flox) mice. Topical administration of hemin via inhalation reduced the dose required to attenuate PMN migration and microvascular permeability by a factor of 40, emphasizing its clinical potential. In addition, HO-1 stimulation was protective against pulmonary inflammation when initiated after the inflammatory stimulus. In conclusion, nonmyeloid HO-1 is crucial for the anti-inflammatory effect of this enzyme on PMN migration to different compartments of the lung and on microvascular permeability.
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Liu B, Qian JM. Cytoprotective role of heme oxygenase-1 in liver ischemia reperfusion injury. Int J Clin Exp Med 2015; 8:19867-19873. [PMID: 26884897 PMCID: PMC4723742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Accepted: 07/03/2015] [Indexed: 06/05/2023]
Abstract
Ischemia/reperfusion (I/R) injury is the main cause of graft dysfunction and failure in vascular occlusion both during liver surgery and during liver transplantation. The pathophysiology of hepatic ischemia-reperfusion includes a number of mechanisms including oxidant stress that contribute to various degrees to the overall organ damage. Heme oxygenases (HO) are essential enzymes which degrade heme into biliverdin-IXalpha, free divalent iron, and carbon monoxide (CO). Due to its anti-inflammatory, anti-apoptotic and, as recently described, anti-viral properties. The inducible HO isoform HO-1 is an important molecule which could find its way into therapy of acute and chronic liver injuries including acute liver failure, alcoholic or viral hepatitis, chronic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma are life threatening diseases and as a consequence might result in the necessity of liver transplantation. Liver transplantation is limited by ischemia/reperfusion (I/R) injury, which is characterized by hypoxia and nutrient deficiency resulting in oxidative stress, apoptosis and immune activation. Induction of HO-1 and application predominantly of CO have been shown to interfere with liver I/R injury and to improve recipient and graft survival. HO-1 and its reaction products of heme degradation has been linked to cytoprotection, and as an inducible form of HO, serves a vital metabolic function as the rate-limiting step in the heme degradation pathway, and affords protection in models of liver I/R injury. HO-1 system is an important player in liver I/R injury condition, and may offer new targets for the management of this condition. This review aims to summarize cytoprotective role of heme oxygenase-1 (HO-1) and its products within the liver.
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Affiliation(s)
- Bin Liu
- Department of General Surgery, Huashan Hospital Affiliated to Fudan University Shanghai 200040, China
| | - Jian-Min Qian
- Department of General Surgery, Huashan Hospital Affiliated to Fudan University Shanghai 200040, China
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Papp Á, Bene Z, Gáspár I, Nagy B, Kádár L, Márialigeti T, Bánfi A, Baktai G, Balla G, Nagy B. Decreased VEGF Level Is Associated with Elevated Ferritin Concentration in Bronchoalveolar Lavage Fluid of Children with Interstitial Lung Diseases. Respiration 2015; 90:443-450. [PMID: 26473738 DOI: 10.1159/000440888] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2015] [Accepted: 09/01/2015] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND A decreased level of vascular endothelial growth factor (VEGF) was previously described in bronchoalveolar lavage fluid (BALF) of adults with interstitial lung diseases (ILD) due to bronchial epithelial cell apoptosis and its proteolytic degradation. Elevated intrapulmonary ferritin was produced by alveolar cells that promoted oxidative injury in such patients. OBJECTIVES In this study, we analyzed the concentrations of VEGF and ferritin in BALF samples of ILD children and studied the relationship between their levels and the degree of inflammation. METHODS BALF and serum concentration of VEGF as well as ferritin and albumin in BALF samples were measured using enzyme-linked immunosorbent assay in children with idiopathic interstitial pneumonia (n = 16), hypersensitivity pneumonitis (n = 11) and idiopathic pulmonary hemosiderosis (n = 3). Twenty-four age- and gender-matched subjects with suspicious foreign body aspiration served as a control group. RESULTS VEGF per albumin levels in BALF were significantly decreased in ILD children compared to controls (1,075 [784-1,415] pg/mg albumin vs. 2,741 [1,131-4,660] pg/mg albumin, p = 0.0008). These values showed a significant negative correlation with inflammatory markers of total immune cell count in BALF (r = -0.411, p = 0.002) and serum C-reactive protein (r = -0.367, p = 0.006). Although serum VEGF was augmented in ILD children versus controls, no difference was observed among the ILD groups. In addition, BALF ferritin/albumin level (688 [188-1,571] ng/mg albumin vs. 256 [178-350] ng/mg albumin, p = 0.022) was significantly higher than normal in ILD individuals, especially in idiopathic pulmonary hemosiderosis. CONCLUSION Depressed VEGF and increased ferritin in BALF may reflect the severity of chronic pulmonary inflammation in altered respiratory epithelium of childhood ILD.
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Affiliation(s)
- Ágnes Papp
- Department of Pediatrics, Clinical Center, University of Debrecen, Debrecen, Hungary
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Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics 2014; 6:748-73. [PMID: 24549403 DOI: 10.1039/c3mt00347g] [Citation(s) in RCA: 411] [Impact Index Per Article: 37.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
"Serum ferritin" presents a paradox, as the iron storage protein ferritin is not synthesised in serum yet is to be found there. Serum ferritin is also a well known inflammatory marker, but it is unclear whether serum ferritin reflects or causes inflammation, or whether it is involved in an inflammatory cycle. We argue here that serum ferritin arises from damaged cells, and is thus a marker of cellular damage. The protein in serum ferritin is considered benign, but it has lost (i.e. dumped) most of its normal complement of iron which when unliganded is highly toxic. The facts that serum ferritin levels can correlate with both disease and with body iron stores are thus expected on simple chemical kinetic grounds. Serum ferritin levels also correlate with other phenotypic readouts such as erythrocyte morphology. Overall, this systems approach serves to explain a number of apparent paradoxes of serum ferritin, including (i) why it correlates with biomarkers of cell damage, (ii) why it correlates with biomarkers of hydroxyl radical formation (and oxidative stress) and (iii) therefore why it correlates with the presence and/or severity of numerous diseases. This leads to suggestions for how one might exploit the corollaries of the recognition that serum ferritin levels mainly represent a consequence of cell stress and damage.
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Affiliation(s)
- Douglas B Kell
- School of Chemistry and The Manchester Institute of Biotechnology, The University of Manchester, 131, Princess St, Manchester M1 7DN, Lancs, UK.
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Konrad FM, Braun S, Ngamsri KC, Vollmer I, Reutershan J. Heme oxygenase-1 attenuates acute pulmonary inflammation by decreasing the release of segmented neutrophils from the bone marrow. Am J Physiol Lung Cell Mol Physiol 2014; 307:L707-17. [DOI: 10.1152/ajplung.00145.2014] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Recruiting polymorphonuclear neutrophil granulocytes (PMNs) from circulation and bone marrow to the site of inflammation is one of the pivotal mechanisms of the innate immune system. During inflammation, the enzyme heme oxygenase 1 (HO-1) has been shown to reduce PMN migration. Although these effects have been described in various models, underlying mechanisms remain elusive. Recent studies revealed an influence of HO-1 on different cells of the bone marrow. We investigated the particular role of the bone marrow in terms of HO-1-dependent pulmonary inflammation. In a murine model of LPS inhalation, stimulation of HO-1 by cobalt (III) protoporphyrin-IX-chloride (CoPP) resulted in reduced segmented PMN migration into the alveolar space. In the CoPP group, segmented PMNs were also decreased intravascularly, and concordantly, mature and immature PMN populations were higher in the bone marrow. Inhibition of the enzyme by tin protoporphyrin-IX increased segmented and banded PMN migration into the bronchoalveolar lavage fluid with enhanced PMN release from the bone marrow and aggravated parameters of tissue inflammation. Oxidative burst activity was significantly higher in immature compared with mature PMNs. The chemokine stromal-derived factor-1 (SDF-1), which mediates homing of leukocytes into the bone marrow and is decreased in inflammation, was increased by CoPP. When SDF-1 was blocked by the specific antagonist AMD3100, HO-1 activation was no longer effective in curbing PMN trafficking to the inflamed lungs. In conclusion, we show evidence that the anti-inflammatory effects of HO-1 are largely mediated by inhibiting the release of segmented PMNs from the bone marrow rather than direct effects within the lung.
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Affiliation(s)
- Franziska M. Konrad
- Department of Anesthesiology and Intensive Care Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Stefan Braun
- Department of Anesthesiology and Intensive Care Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Kristian-Christos Ngamsri
- Department of Anesthesiology and Intensive Care Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Irene Vollmer
- Department of Anesthesiology and Intensive Care Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Jörg Reutershan
- Department of Anesthesiology and Intensive Care Medicine, University Hospital of Tübingen, Tübingen, Germany
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Liao YF, Zhu W, Li DP, Zhu X. Heme oxygenase-1 and gut ischemia/reperfusion injury: A short review. World J Gastroenterol 2013; 19:3555-3561. [PMID: 23801856 PMCID: PMC3691047 DOI: 10.3748/wjg.v19.i23.3555] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Revised: 01/19/2013] [Accepted: 04/11/2013] [Indexed: 02/06/2023] Open
Abstract
Ischemia/reperfusion (I/R) injury of the gut is a significant problem in a variety of clinical settings and is associated with a high morbidity and mortality. Although the mechanisms involved in the pathogenesis of gut I/R injury have not been fully elucidated, it is generally believed that oxidative stress with subsequent inflammatory injury plays an important role. Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme, followed by production of CO, biliverdin, and free iron. The HO system is believed to confer cytoprotection by inhibiting inflammation, oxidation, and apoptosis, and maintaining microcirculation. HO-1, an inducible form of HO, serves a vital metabolic function as the rate-limiting step in the heme degradation pathway, and affords protection in models of intestinal I/R injury. HO-1 system is an important player in intestinal I/R injury condition, and may offer new targets for the management of this condition.
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Liu K, Chen HL, Huang H, Jing H, Dong GH, Wu HW, You QS. Curcumin attenuates cardiopulmonary bypass-induced lung oxidative damage in rats. J Cardiovasc Pharmacol Ther 2012; 17:395-402. [PMID: 22492920 DOI: 10.1177/1074248412442002] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Acute lung injury is a common complication after cardiopulmonary bypass (CPB). Oxidative damage greatly impacts CPB-induced lung ischemic pathogenesis and may represent a target for treatment. We aimed to investigate whether curcumin upregulates heme oxygenase 1 (HO-1) expression and ameliorates lung injury in a rat CPB model. METHODS A total of 80 male Sprague-Dawley rats were divided into 2 sets of 5 groups (n = 8 per group): sham; control (CPB); vehicle; low-dose curcumin (L-Cur); and high-dose curcumin (H-Cur). Animals were pretreated with a single intraperitoneal injection of vehicle, L-Cur (50 mg/kg), or H-Cur (200 mg/kg) 2 hours prior to CPB. Lung tissue, serum, and bronchoalveolar lavage fluid was harvested 2 or 24 hours postoperatively. In the control group, CPB-induced lung injury was confirmed by histopathologic examination and a significantly increased wet-to-dry lung weight ratio and pulmonary permeability index value was observed (P < .05 vs sham group). Cardiopulmonary bypass was associated with a marked rise in the level of malondialdehyde and myeloperoxidase and a fall in superoxide dismutase 2 and 24 hours after surgery (P < .05 vs sham group). Administration of curcumin ameliorated lung damage and reversed the oxidative stress markers in a partially dose-dependent manner (P < .05 vs vehicle group). Furthermore, HO-1 gene transcription and protein expression were elevated to a greater extent in the lungs after curcumin pretreatment compared with the vehicle pretreatment. CONCLUSIONS Curcumin has the potential to provide protection from CPB-induced lung damage reflected in the expression of oxidative stress markers. The antioxidant effect of curcumin may be partly related to upregulation of HO-1.
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Affiliation(s)
- Kun Liu
- Department of Cardiothoracic Surgery, The Affiliated Hospital of Nantong University, Nantong City, Jiangsu Province, China
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