Regulation of Mitochondrial Quality Control by Natural Drugs in the Treatment of Cardiovascular Diseases: Potential and Advantages

Chang, Xing; Zhang, Wenjin; Zhao, Zhenyu; Ma, Chunxia; Zhang, Tian; Qing, Meng; Yan, Peizheng; Zhang, Lei; Zhao, Yong

doi:10.3389/fcell.2020.616139

Cited by 36 publications

(33 citation statements)

References 202 publications

(167 reference statements)

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“…Mitochondrial dysfunction is an important contributor to the pathogenesis of myocardial stress, together with oxidative stress, protein misfolding, and inactive protein denaturation ( Zhou et al, 2017a ; Kobayashi et al, 2020 ; Ma et al, 2020b ; Wang et al, 2020b , c ). The accumulation of reactive oxygen species promotes the mutation of mitochondrial DNA ( Wang et al, 2019a ; Chang et al, 2020 ; Szaraz et al, 2020 ), while the disruption of the tricarboxylic acid cycle depletes the cellular energy supply and accelerates cellular aging ( Cao et al, 2019 ; Mukwaya et al, 2019 ). Myocardial stress can lead to myocardial cardiac ischemia, myocardial infarction, hyperglycemia-induced myocardial damage, and pressure load-induced myocardial injury ( Zhou et al, 2019a ; Ajoolabady et al, 2020 ; Jusic and Devaux, 2020 ; Santin et al, 2020 ; Wang et al, 2020g ; Zhou et al, 2020c ).…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

Kimberlee

et al. 2021

Front. Physiol.

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A variety of complex risk factors and pathological mechanisms contribute to myocardial stress, which ultimately promotes the development of cardiovascular diseases, including acute cardiac insufficiency, myocardial ischemia, myocardial infarction, high-glycemic myocardial injury, and acute alcoholic cardiotoxicity. Myocardial stress is characterized by abnormal metabolism, excessive reactive oxygen species production, an insufficient energy supply, endoplasmic reticulum stress, mitochondrial damage, and apoptosis. Mitochondria, the main organelles contributing to the energy supply of cardiomyocytes, are key determinants of cell survival and death. Mitophagy is important for cardiomyocyte function and metabolism because it removes damaged and aged mitochondria in a timely manner, thereby maintaining the proper number of normal mitochondria. In this review, we first introduce the general characteristics and regulatory mechanisms of mitophagy. We then describe the three classic mitophagy regulatory pathways and their involvement in myocardial stress. Finally, we discuss the two completely opposite effects of mitophagy on the fate of cardiomyocytes. Our summary of the molecular pathways underlying mitophagy in myocardial stress may provide therapeutic targets for myocardial protection interventions.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

Kimberlee

et al. 2021

Front. Physiol.

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“…Many studies have reported that these drugs have the pharmacological effects of antioxidative stress and regulating MQC. In the process of high-lipid, high-glucose, or anoxia-induced redox imbalance or mitochondrial dysfunction, it can have a good protective effect on cells [ 48 ]. Our previous study found that astragaloside IV can increase the expression of HCN4 in injured SANCs of newborn rabbits, protect the damaged cytoskeleton, and improve the survival level of SANCs [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Tongyang Huoxue Decoction (TYHX) Ameliorating Hypoxia/Reoxygenation‐Induced Disequilibrium of Calcium Homeostasis and Redox Imbalance via Regulating Mitochondrial Quality Control in Sinoatrial Node Cells

Chang

Yao

et al. 2021

Oxidative Medicine and Cellular Longevity

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Sick sinus syndrome (SSS) is a disease with bradycardia or arrhythmia. The pathological mechanism of SSS is mainly due to the abnormal conduction function of the sinoatrial node (SAN) caused by interstitial lesions or fibrosis of the SAN or surrounding tissues, SAN pacing dysfunction, and SAN impulse conduction accompanied by SAN fibrosis. Tongyang Huoxue Decoction (TYHX) is widely used in SSS treatment and amelioration of SAN fibrosis. It has a variety of active ingredients to regulate the redox balance and mitochondrial quality control. This study mainly discusses the mechanism of TYHX in ameliorating calcium homeostasis disorder and redox imbalance of sinoatrial node cells (SANCs) and clarifies the protective mechanism of TYHX on the activity of SANCs. The activity of SANCs was determined by CCK-8 and the TUNEL method. The levels of apoptosis, ROS, and calcium release were analyzed by flow cytometry and immunofluorescence. The mRNA and protein levels of calcium channel regulatory molecules and mitochondrial quality control-related molecules were detected by real-time quantitative PCR and Western Blot. The level of calcium release was detected by laser confocal. It was found that after H/R treatment, the viability of SANCs decreased significantly, the levels of apoptosis and ROS increased, and the cells showed calcium overload, redox imbalance, and mitochondrial dysfunction. After treatment with TYHX, the cell survival level was improved, calcium overload and oxidative stress were inhibited, and mitochondrial energy metabolism and mitochondrial function were restored. However, after the SANCs were treated with siRNA (si-β-tubulin), the regulation of TYHX on calcium homeostasis and redox balance was counteracted. These results suggest that β-tubulin interacts with the regulation of mitochondrial function and calcium release. TYHX may regulate mitochondrial quality control, maintain calcium homeostasis and redox balance, and protect SANCs through β-tubulin. The regulation mechanism of TYHX on mitochondrial quality control may also become a new target for SSS treatment.

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“…ROS can also damage actin and excitatory-contractile coupling proteins, resulting in cardiac muscle systolic/diastolic dysfunction. Moreover, insufficient ATP synthesis leads to a lack of energy supply to cardiomyocytes, which has serious adverse effects on cardiomyocyte survival and cardiac ejection function [53].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, severe diabetic cardiomyopathy with heart failure is accompanied by myocardial hypertrophy, partial myocardial ischemia, and hypoxia [36,53]. The energy metabolism of myocardial cells is converted from fatty acid oxidation to glycolysis to adapt to hypoxia as a selfprotective mechanism.…”

Section: Discussionmentioning

confidence: 99%

SIRT5‐Related Desuccinylation Modification Contributes to Quercetin‐Induced Protection against Heart Failure and High‐Glucose‐Prompted Cardiomyocytes Injured through Regulation of Mitochondrial Quality Surveillance

Chang

Zhang

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Myocardial fibrosis represents the primary pathological change associated with diabetic cardiomyopathy and heart failure, and it leads to decreased myocardial compliance with impaired cardiac diastolic and systolic function. Quercetin, an active ingredient in various medicinal plants, exerts therapeutic effects against cardiovascular diseases. Here, we investigate whether SIRT5- and IDH2-related desuccinylation is involved in the underlying mechanism of myocardial fibrosis in heart failure while exploring related therapeutic drugs for mitochondrial quality surveillance. Mouse models of myocardial fibrosis and heart failure, established by transverse aortic constriction (TAC), were administered with quercetin (50 mg/kg) daily for 4 weeks. HL-1 cells were pretreated with quercetin and treated with high glucose (30 mM) in vitro. Cardiac function, western blotting, quantitative PCR, enzyme-linked immunosorbent assay, and immunofluorescence analysis were employed to analyze mitochondrial quality surveillance, oxidative stress, and inflammatory response in myocardial cells, whereas IDH2 succinylation levels were detected using immunoprecipitation. Myocardial fibrosis and heart failure incidence increased after TAC, with abnormal cardiac ejection function. Following high-glucose treatment, HL-1 cell activity was inhibited, causing excess production of reactive oxygen species and inhibition of mitochondrial respiratory complex I/III activity and mitochondrial antioxidant enzyme activity, as well as increased oxidative stress and inflammatory response, imbalanced mitochondrial quality surveillance and homeostasis, and increased apoptosis. Quercetin inhibited myocardial fibrosis and improved cardiac function by increasing mitochondrial energy metabolism and regulating mitochondrial fusion/fission and mitochondrial biosynthesis while inhibiting the inflammatory response and oxidative stress injury. Additionally, TAC inhibited SIRT5 expression at the mitochondrial level and increased IDH2 succinylation. However, quercetin promoted the desuccinylation of IDH2 by increasing SIRT5 expression. Moreover, treatment with si-SIRT5 abolished the protective effect of quercetin on cell viability. Hence, quercetin may promote the desuccinylation of IDH2 through SIRT5, maintain mitochondrial homeostasis, protect mouse cardiomyocytes under inflammatory conditions, and improve myocardial fibrosis, thereby reducing the incidence of heart failure.

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Regulation of Mitochondrial Quality Control by Natural Drugs in the Treatment of Cardiovascular Diseases: Potential and Advantages

Cited by 36 publications

References 202 publications

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

[Retracted] Tongyang Huoxue Decoction (TYHX) Ameliorating Hypoxia/Reoxygenation‐Induced Disequilibrium of Calcium Homeostasis and Redox Imbalance via Regulating Mitochondrial Quality Control in Sinoatrial Node Cells

SIRT5‐Related Desuccinylation Modification Contributes to Quercetin‐Induced Protection against Heart Failure and High‐Glucose‐Prompted Cardiomyocytes Injured through Regulation of Mitochondrial Quality Surveillance

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