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.

scholarly journals Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?

2021 ◽  
Vol 9 ◽  
Author(s):  
Jia-Yue Duan ◽  
Xiao Lin ◽  
Feng Xu ◽  
Su-Kang Shan ◽  
Bei Guo ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Vital Role ◽  
Lipid Hydroperoxides ◽  
Regulated Cell Death ◽  
Metabolic Bone ◽  
Dependent Form ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Ferroptosis is classified as an iron-dependent form of regulated cell death (RCD) attributed to the accumulation of lipid hydroperoxides and redox imbalance. In recent years, accumulating researches have suggested that ferroptosis may play a vital role in the development of diverse metabolic diseases, for example, diabetes and its complications (e.g., diabetic nephropathy, diabetic cardiomyopathy, diabetic myocardial ischemia/reperfusion injury and atherosclerosis [AS]), metabolic bone disease and adrenal injury. However, the specific physiopathological mechanism and precise therapeutic effect is still not clear. In this review, we summarized recent advances about the development of ferroptosis, focused on its potential character as the therapeutic target in metabolic diseases, and put forward our insights on this topic, largely to offer some help to forecast further directions.

scholarly journals Nrf2 as a Key Player of Redox Regulation in Cardiovascular Diseases

2016 ◽  
pp. S1-S10 ◽  
Author(s):  
M. BARANČÍK ◽  
L. GREŠOVÁ ◽  
M. BARTEKOVÁ ◽  
I. DOVINOVÁ
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Redox Regulation ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Redox Homeostasis ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

The oxidative stress plays an important role in the development of cardiovascular diseases (CVD). In CVD progression an aberrant redox regulation was observed. In this regulation levels of reactive oxygen species (ROS) play an important role in cellular signaling, where Nrf2 is the key regulator of redox homeostasis. Keap1-Nrf2-ARE system regulates a great set of detoxificant and antioxidant enzymes in cells after ROS and electrophiles exposure. In this review we focus on radical-generating systems in cardiovascular system as well as on Nrf2 as a target against oxidative stress and a key player of redox regulation in cardiovascular diseases. We also summarize the current knowledge about the role of Nrf2 in pathophysiology of several CVD (hypertension, cardiac hypertrophy, cardiomyopathies) as well as in cardioprotection against myocardial ischemia/ reperfusion injury.

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 New Developments in Exosomal lncRNAs in Cardiovascular Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhu Yuan ◽  
Weiqiang Huang
Keyword(s):  
Cardiovascular Diseases ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Types ◽  
Research Progress ◽  
Therapeutic Effects ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Non Coding Rnas ◽  
Myocardial Ischemia Reperfusion ◽  
Rheumatic Heart

Long non-coding RNAs (lncRNAs) are non-coding RNAs with lengths >200 nt and are involved in the occurrence and development of cardiovascular diseases (CVDs). Exosomes are secreted and produced by various cell types. Exosome contents include various ncRNAs, proteins and lipids. Exosomes are also important mediators of intercellular communication. The proportion of lncRNAs in exosomes is low, but increasing evidence suggests that exosomal lncRNAs play important roles in CVDs. We focused on research progress in exosomal lncRNAs in atherosclerosis, myocardial infarction, myocardial ischemia-reperfusion injury, cardiac angiogenesis, cardiac aging, rheumatic heart disease, and chronic kidney disease combined with CVD. The potential diagnostic and therapeutic effects of exosomal lncRNAs in CVDs are summarized based on preclinical studies involving animal and cell models and circulating exosomes in clinical patients. Finally, the challenges and possible prospects of exosomes and exosomal lncRNAs in clinical applications related to CVD are discussed.

scholarly journals RCAN1 in cardiovascular diseases: molecular mechanisms and a potential therapeutic target

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Shuai Wang ◽  
Yuqing Wang ◽  
Kaixin Qiu ◽  
Jin Zhu ◽  
Yili Wu
Keyword(s):  
Cardiovascular Diseases ◽  
Myocardial Hypertrophy ◽  
Ischemia Reperfusion Injury ◽  
Aortic Rupture ◽  
Ischemia Reperfusion ◽  
Intramural Hematoma ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Underlying Mechanisms

AbstractCardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Considerable efforts are needed to elucidate the underlying mechanisms for the prevention and treatment of CVDs. Regulator of calcineurin 1 (RCAN1) is involved in both development/maintenance of the cardiovascular system and the pathogenesis of CVDs. RCAN1 reduction protects against atherosclerosis by reducing the uptake of oxidized low-density lipoproteins, whereas RCAN1 has a protective effect on myocardial ischemia/reperfusion injury, myocardial hypertrophy and intramural hematoma/aortic rupture mainly mediated by maintaining mitochondrial function and inhibiting calcineurin and Rho kinase activity, respectively. In this review, the regulation and the function of RCAN1 are summarized. Moreover, the dysregulation of RCAN1 in CVDs is reviewed. In addition, the beneficial role of RCAN1 reduction in atherosclerosis and the protective role of RCAN1 in myocardial ischemia/reperfusion injury, myocardial hypertrophy and intramural hematoma /aortic rupture are discussed, as well as underlying mechanisms. Furthermore, the therapeutic potential and challenges of targeting RCAN1 for CVDs treatment are also discussed.

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.

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