scholarly journals Iron in Cardiovascular Disease: Challenges and Potentials

2021 ◽  
Vol 8 ◽  
Author(s):  
Shizhen Li ◽  
Xiangyu Zhang
Keyword(s):  
Cardiovascular Disease ◽  
Cell Death ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Iron Chelation ◽  
Medical Intervention ◽  
Atherosclerotic Cardiovascular Disease ◽  
Dependent Cell ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Iron is essential for many biological processes. Inadequate or excess amount of body iron can result in various pathological consequences. The pathological roles of iron in cardiovascular disease (CVD) have been intensively studied for decades. Convincing data demonstrated a detrimental effect of iron deficiency in patients with heart failure and pulmonary arterial hypertension, but it remains unclear for the pathological roles of iron in other cardiovascular diseases. Meanwhile, ferroptosis is an iron-dependent cell death that is distinct from apoptosis, necroptosis, and other types of cell death. Ferroptosis has been reported in several CVDs, namely, cardiomyopathy, atherosclerotic cardiovascular disease, and myocardial ischemia/reperfusion injury. Iron chelation therapy seems to be an available strategy to ameliorate iron overload-related disorders. It is still a challenge to accurately clarify the pathological roles of iron in CVD and search for effective medical intervention. In this review, we aim to summarize the pathological roles of iron in CVD, and especially highlight the potential mechanism of ferroptosis in these diseases.

Severity of myocardial injury following ischemia-reperfusion is increased in a mouse model of allergic asthma

2007 ◽  
Vol 292 (1) ◽  
pp. H572-H579 ◽  
Author(s):  
Surovi Hazarika ◽  
Michael R. Van Scott ◽  
Robert M. Lust
Keyword(s):  
Cardiovascular Disease ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Vasculature ◽  
Enhanced Expression ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Cardiovascular disease is common in asthmatic patients but often is attributed to respiratory drug therapy. With mounting evidence for an inflammatory role in the development of cardiovascular disease, we hypothesized that the inflammation associated with asthma adversely affects the cardiovascular system independent of therapeutic interventions. The hypothesis was tested in a murine model of myocardial ischemia-reperfusion injury. BALB/C mice were sensitized by intraperitoneal injection of ragweed (RW) or normal saline (NS) and challenged by intratracheal instillation of RW or NS. Effective allergic sensitization and challenge were confirmed by hyperresponsiveness to aerosolized methacholine and bronchoalveolar lavage. In vivo myocardial ischemia-reperfusion injury was induced by ligation of the left anterior descending artery for 20 min, followed by reperfusion for 2 h. The infarct size (% risk area) and neutrophil density in the myocardial area at risk were significantly higher in the RW/RW group than in the control groups. The tissue neutrophil count correlated with the infarct size but did not correlate with blood neutrophil counts. Furthermore, in the RW/RW group, circulating granulocytes showed an enhanced expression of CD11b and P-selectin glycoprotein ligand-1, enhanced stimulated release of myeloperoxidase, and enhanced expression of P-selectin in the coronary vasculature. These results indicate that allergic responses in the airways enhance expression of attachment molecules in coronary vasculature and activate circulating neutrophils, resulting in recruitment of highly activated neutrophils to the infarct zone during an acute ischemia-reperfusion event, thereby enhancing tissue destruction.

Abstract 213: Disruption of Mitochondrial Cristae Integrity in Lethal Myocardial Ischemia-Reperfusion Injury: Association or Cause-and-Effect?

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Andrew R Kulek ◽  
Vishnu V.R. Undyala ◽  
Sarita Raghunayakula ◽  
Thomas H Sanderson ◽  
Karin Przyklenk
Keyword(s):  
Cell Death ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Period ◽  
Fold Increase ◽  
Inner Mitochondrial Membrane ◽  
Cause And Effect ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Mitochondrial Membrane Protein

Background: Considerable attention has focused on the concept that disruption of mitochondrial structure/function is a determinant of cell death in cardiomyocytes subjected to ischemia-reperfusion (IR). However, the details of this relationship, and the precise mitochondrial event(s) that precipitate lethal IR injury, remain unresolved. Aim: Emerging evidence has revealed that cardiomyocytes subjected to IR display: i) degradation of optic atrophy protein-1 (OPA1), the inner mitochondrial membrane protein responsible for maintaining cristae junction integrity, followed by ii) inappropriate release of OPA1 into the cytosol. Accordingly, our goal was to establish whether degradation of OPA1 plays a causal, mechanistic role in determining cardiomyocyte fate. Methods and Results: In Protocol 1 , HL-1 cardiomyocytes underwent 2.5 hrs of simulated ischemia. This was preceded by either a classic intervention known to attenuate IR injury (ischemic preconditioning: IPC) or a matched control period. Cell viability was quantified at 24 hrs post-R, and release of OPA1 into the cytosol was measured at 30 min post-R. In Controls, IR resulted in ~50% cell death and a >15-fold increase in OPA1 in the cytosol - effects that were both attenuated by IPC (Figure: top). In Protocol 2 : to discern whether these data reflect an association between OPA1 degradation and cell death or cause-and-effect , HL-1 cells were transfected with either siRNA targeting OPA1 (resulting in near-total knockdown of OPA1 expression: data not shown) or scrambled siRNA. Cardiomyocytes then underwent IPC/no intervention and IR as in Protocol 1. If OPA1 disruption contributes to IR injury, we reasoned that OPA1 knockdown would exacerbate cell death in Controls and attenuate IPC-mediated protection. However, OPA1 knockdown had no effect on cell death in either cohort (Figure: bottom). Conclusion: Disruption of OPA1 and loss of cristae junction integrity does not play a causal role in lethal IR injury.

scholarly journals Targeting Ferroptosis to Treat Cardiovascular Diseases: A New Continent to Be Explored

2021 ◽  
Vol 9 ◽  
Author(s):  
Fangze Huang ◽  
Ronghua Yang ◽  
Zezhou Xiao ◽  
Yu Xie ◽  
Xuefeng Lin ◽  
...  
Keyword(s):  
Cell Death ◽  
Cardiovascular Diseases ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glutamine Metabolism ◽  
Lipid Hydroperoxides ◽  
Genetic Manipulations ◽  
Regulated Cell Death ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Cardiovascular diseases, including cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, vascular injury, stroke, and arrhythmia, are correlated with cardiac and vascular cell death. Ferroptosis is a novel form of non-apoptotic regulated cell death which is characterized by an iron-driven accumulation of lethal lipid hydroperoxides. The initiation and execution of ferroptosis are under the control of several mechanisms, including iron metabolism, glutamine metabolism, and lipid peroxidation. Recently, emerging evidence has demonstrated that ferroptosis can play an essential role in the development of various cardiovascular diseases. Recent researches have shown the ferroptosis inhibitors, iron chelators, genetic manipulations, and antioxidants can alleviate myocardial injury by blocking ferroptosis pathway. In this review, we systematically described the mechanisms of ferroptosis and discussed the role of ferroptosis as a novel therapeutic strategy in the treatment of cardiovascular diseases.

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