Dual Role of Mitophagy in Cardiovascular Diseases

Li, Yibo; Meng, Wei-zheng; Hou, Yaxin; Li, Dongxu; Wang, Xiulong; Wu, Kai; Sun, Siyu; Liu, Huibing; Li, Xuefang; Lin, Fei; Zhao, Guoan

doi:10.1097/fjc.0000000000001046

Cited by 13 publications

(11 citation statements)

References 98 publications

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“…In the aging heart, reduced mitophagy was related to accumulation of injured mitochondria, which produce a large amount of ROS. During ischemic damage or cardiac hypertrophy, mitophagy is essential to clear defective mitochondria and avoid oxidative damage [ 180 ]. As previously reported, increased oxidative stress contributes to a vicious cycle between the presence of damaged mitochondria and increased ROS production [ 44 , 181 ].…”

Section: Aging Mitochondriamentioning

confidence: 99%

The Role of Oxidative Stress in the Aging Heart

et al. 2022

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Medical advances and the availability of diagnostic tools have considerably increased life expectancy and, consequently, the elderly segment of the world population. As age is a major risk factor in cardiovascular disease (CVD), it is critical to understand the changes in cardiac structure and function during the aging process. The phenotypes and molecular mechanisms of cardiac aging include several factors. An increase in oxidative stress is a major player in cardiac aging. Reactive oxygen species (ROS) production is an important mechanism for maintaining physiological processes; its generation is regulated by a system of antioxidant enzymes. Oxidative stress occurs from an imbalance between ROS production and antioxidant defenses resulting in the accumulation of free radicals. In the heart, ROS activate signaling pathways involved in myocyte hypertrophy, interstitial fibrosis, contractile dysfunction, and inflammation thereby affecting cell structure and function, and contributing to cardiac damage and remodeling. In this manuscript, we review recent published research on cardiac aging. We summarize the aging heart biology, highlighting key molecular pathways and cellular processes that underlie the redox signaling changes during aging. Main ROS sources, antioxidant defenses, and the role of dysfunctional mitochondria in the aging heart are addressed. As metabolism changes contribute to cardiac aging, we also comment on the most prevalent metabolic alterations. This review will help us to understand the mechanisms involved in the heart aging process and will provide a background for attractive molecular targets to prevent age-driven pathology of the heart. A greater understanding of the processes involved in cardiac aging may facilitate our ability to mitigate the escalating burden of CVD in older individuals and promote healthy cardiac aging.

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Section: Aging Mitochondriamentioning

confidence: 99%

The Role of Oxidative Stress in the Aging Heart

et al. 2022

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“…EC-intrinsic autophagy is suggested to enable ECs to adjust plastically to various insulting stressors [85,90,93] and leads to autophagic cell death in severely damaged ECs [94][95][96]. Indeed, various studies have suggested that the EC-autophagic flux facilitates the pathogenesis of CMD in diverse CVDs, including ischemic heart disease, DCM, hypertrophy cardiomyopathy, heart failure, and inflammatory disorders [9,10,[12][13][14][15][16]. However, the detailed role of autophagy in adjusting EC reactions is still controversial and seems to depend on the particular type of metabolic insults or the disease-associated microenvironment.…”

Section: Coronary Endothelial Autophagy In Cvdsmentioning

confidence: 99%

“…Autophagy is a critical regulator of cardiac metabolism and homeostasis [8][9][10]. Deficient or uncontrolled activation of endothelial autophagy is associated with the onset and development of diverse cardiovascular diseases (CVDs), including CMD [9][10][11][12][13][14][15][16]. Understanding the molecular basis of endothelial autophagy in CMD is crucial for the discovery of novel regulatory mechanisms and the identification of new diagnostic and therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Endothelial Autophagy in Coronary Microvascular Dysfunction and Cardiovascular Disease

Zhao

Satyanarayana

Zhang

et al. 2022

Cells

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Coronary microvascular dysfunction (CMD) refers to a subset of structural and/or functional disorders of coronary microcirculation that lead to impaired coronary blood flow and eventually myocardial ischemia. Amid the growing knowledge of the pathophysiological mechanisms and the development of advanced tools for assessment, CMD has emerged as a prevalent cause of a broad spectrum of cardiovascular diseases (CVDs), including obstructive and nonobstructive coronary artery disease, diabetic cardiomyopathy, and heart failure with preserved ejection fraction. Of note, the endothelium exerts vital functions in regulating coronary microvascular and cardiac function. Importantly, insufficient or uncontrolled activation of endothelial autophagy facilitates the pathogenesis of CMD in diverse CVDs. Here, we review the progress in understanding the pathophysiological mechanisms of autophagy in coronary endothelial cells and discuss their potential role in CMD and CVDs.

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“…Mitophagy promotes mitochondrial turnover and prevents the accumulation of dysfunctional organelles. A moderate amount of mitophagy can prevent endothelial cell damage and avoid further CVD development [ 66 ].…”

Section: Nrf2 Suppresses Endothelial Dysfunction By Improving Mitocho...mentioning

confidence: 99%

The Beneficial Role of Nrf2 in the Endothelial Dysfunction of Atherosclerosis

Huang

Zeng

et al. 2022

Cardiology Research and Practice

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Cardiovascular disease (CVD) is a serious public health issue in China, accounting for more than 40% of all mortality, and it is the leading cause of death worldwide. Atherosclerosis is the pathological basis for much CVD, including coronary heart disease, acute myocardial infarction, and stroke. Endothelial dysfunction is an initiating and exacerbating factor in atherosclerosis. Recent research has linked oxidative stress and mitochondrial damage to endothelial dysfunction. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor with antioxidant effects that is strongly connected to several CVDs. However, the mechanism by which Nrf2 reduces CVD is unknown. Research indicates that Nrf2 improves endothelial function by resisting oxidative stress and mitochondrial damage, thereby delaying atherosclerosis. This article examines the mechanisms and potential targets of Nrf2 affecting endothelial cell function to improve atherosclerosis and to provide ideas for the development of new CVD treatments.

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Dual Role of Mitophagy in Cardiovascular Diseases

Cited by 13 publications

References 98 publications

The Role of Oxidative Stress in the Aging Heart

The Role of Oxidative Stress in the Aging Heart

Endothelial Autophagy in Coronary Microvascular Dysfunction and Cardiovascular Disease

The Beneficial Role of Nrf2 in the Endothelial Dysfunction of Atherosclerosis

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