Mitophagy Receptors and Mediators: Therapeutic Targets in the Management of Cardiovascular Ageing

Ajoolabady, Amir; Aslkhodapasandhokmabad, Hamid; Aghanejad, Ayuob; Zhang, Yingmei; Ren, Jun

doi:10.1016/j.arr.2020.101129

Cited by 75 publications

(47 citation statements)

References 219 publications

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“…It seems plausible that there may be a mechanism that mitigates the harmful effects of mitochondrial fission and helps maintain mitochondrial health. Mitophagy, which is primarily triggered by elevated mtROS levels, is the main safeguard mechanism against disrupted mitochondrial homeostasis (Frank et al, 2012;Ajoolabady et al, 2020;Schofield and Schafer, 2020;Wang et al, 2020d). Mitophagy is a selective autophagic process for the removal of the damaged mitochondria and is vital for cell survival.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Mitochondrial Fission and Mitophagy Reciprocally Orchestrate Cardiac Fibroblasts Activation

Gao

Zhang

Tao

et al. 2021

Front. Cell Dev. Biol.

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Although mitochondrial fission has been reported to increase proliferative capacity and collagen production, it can also contribute to mitochondrial impairment, which is detrimental to cell survival. The aim of the present study was to investigate the role of mitochondrial fission in cardiac fibroblasts (CF) activation and explore the mechanisms involved in the maintenance of mitochondrial health under this condition. For this, changes in the levels of mitochondrial fission/fusion-related proteins were assessed in transforming growth factor beta 1 (TGF-β1)-activated CF, whereas the role of mitochondrial fission during this process was also elucidated, as were the underlying mechanisms. The interaction between mitochondrial fission and mitophagy, the main defense mechanism against mitochondrial impairment, was also explored. The results showed that the mitochondria in TGF-β1-treated CF were noticeably more fragmented than those of controls. The expression of several mitochondrial fission-related proteins was markedly upregulated, and the levels of fusion-related proteins were also altered, but to a lesser extent. Inhibiting mitochondrial fission resulted in a marked attenuation of TGF-β1-induced CF activation. The TGF-β1-induced increase in glycolysis was greatly suppressed in the presence of a mitochondrial inhibitor, whereas a glycolysis-specific antagonist exerted little additional antifibrotic effects. TGF-β1 treatment increased cellular levels of reactive oxygen species (ROS) and triggered mitophagy, but this effect was reversed following the application of ROS scavengers. For the signals mediating mitophagy, the expression of Pink1, but not Bnip3l/Nix or Fundc1, exhibited the most significant changes, which could be counteracted by treatment with a mitochondrial fission inhibitor. Pink1 knockdown suppressed CF activation and mitochondrial fission, which was accompanied by increased CF apoptosis. In conclusion, mitochondrial fission resulted in increased glycolysis and played a crucial role in CF activation. Moreover, mitochondrial fission promoted reactive oxygen species (ROS) production, leading to mitophagy and the consequent degradation of the impaired mitochondria, thus promoting CF survival and maintaining their activation.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Mitochondrial Fission and Mitophagy Reciprocally Orchestrate Cardiac Fibroblasts Activation

Gao

Zhang

Tao

et al. 2021

Front. Cell Dev. Biol.

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“…Autophagy could promote the clearance of impaired cellular organelles (mitochondria, endoplasmic reticulum, etc.) and dysfunctional proteins, which contributes to the life extension and antiaging effect [21,22]. A study demonstrated that resveratrol could induce autophagy in human cells in vitro and Caenorhabditis elegans in vivo and prolong lifespan in Caenorhabditis elegans, while this effect was prevented under the condition of knockdown or knockout of sirtuin (Sirt)1.…”

Section: Effect Of Resveratrol On Life Extensionmentioning

confidence: 99%

Effects and Mechanisms of Resveratrol on Aging and Age‐Related Diseases

Zhou

Luo

Huang

et al. 2021

Oxidative Medicine and Cellular Longevity

186

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The aging of population has become an issue of great concern because of its rapid increase. Aging is an important risk factor of many chronic diseases. Resveratrol could be found in many foods, such as grapes, red wine, peanuts, and blueberries. Many studies reported that resveratrol possessed various bioactivities, such as antioxidant, anti-inflammatory, cardiovascular protection, anticancer, antidiabetes mellitus, antiobesity, neuroprotection, and antiaging effects. The antiaging mechanisms of resveratrol were mainly ameliorating oxidative stress, relieving inflammatory reaction, improving mitochondrial function, and regulating apoptosis. Resveratrol could be an effective and safe compound for the prevention and treatment of aging and age-related diseases. In this review, we summarize the effects of resveratrol on aging, life extension, and several age-related diseases, with special attention paid to the mechanisms of antiaging action.

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“…Aging is one of the major risk factors for developing multi morbidity and HFpEF, and both multi morbidity and HFpEF are unmet needs in the therapy of HF (131)(132)(133). The main underlying mechanisms of cardiovascular aging are associated with mitochondrial metabolism (134,135), chronic inflammation (136), autophagy (137), and oxidative stress (138).…”

Section: Major Shared Risk Factors Of Hf and Comorbidities Are Associated With Metabolism And Inflammationmentioning

confidence: 99%

Metabolism and Chronic Inflammation: The Links Between Chronic Heart Failure and Comorbidities

Zhao

Wang

2021

Front. Cardiovasc. Med.

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Heart failure (HF) patients often suffer from multiple comorbidities, such as diabetes, atrial fibrillation, depression, chronic obstructive pulmonary disease, and chronic kidney disease. The coexistance of comorbidities usually leads to multi morbidity and poor prognosis. Treatments for HF patients with multi morbidity are still an unmet clinical need, and finding an effective therapy strategy is of great value. HF can lead to comorbidity, and in return, comorbidity may promote the progression of HF, creating a vicious cycle. This reciprocal correlation indicates there may be some common causes and biological mechanisms. Metabolism remodeling and chronic inflammation play a vital role in the pathophysiological processes of HF and comorbidities, indicating metabolism and inflammation may be the links between HF and comorbidities. In this review, we comprehensively discuss the major underlying mechanisms and therapeutic implications for comorbidities of HF. We first summarize the potential role of metabolism and inflammation in HF. Then, we give an overview of the linkage between common comorbidities and HF, from the perspective of epidemiological evidence to the underlying metabolism and inflammation mechanisms. Moreover, with the help of bioinformatics, we summarize the shared risk factors, signal pathways, and therapeutic targets between HF and comorbidities. Metabolic syndrome, aging, deleterious lifestyles (sedentary behavior, poor dietary patterns, smoking, etc.), and other risk factors common to HF and comorbidities are all associated with common mechanisms. Impaired mitochondrial biogenesis, autophagy, insulin resistance, and oxidative stress, are among the major mechanisms of both HF and comorbidities. Gene enrichment analysis showed the PI3K/AKT pathway may probably play a central role in multi morbidity. Additionally, drug targets common to HF and several common comorbidities were found by network analysis. Such analysis has already been instrumental in drug repurposing to treat HF and comorbidity. And the result suggests sodium-glucose transporter-2 (SGLT-2) inhibitors, IL-1β inhibitors, and metformin may be promising drugs for repurposing to treat multi morbidity. We propose that targeting the metabolic and inflammatory pathways that are common to HF and comorbidities may provide a promising therapeutic strategy.

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Mitophagy Receptors and Mediators: Therapeutic Targets in the Management of Cardiovascular Ageing

Cited by 75 publications

References 219 publications

RETRACTED: Mitochondrial Fission and Mitophagy Reciprocally Orchestrate Cardiac Fibroblasts Activation

RETRACTED: Mitochondrial Fission and Mitophagy Reciprocally Orchestrate Cardiac Fibroblasts Activation

Effects and Mechanisms of Resveratrol on Aging and Age‐Related Diseases

Metabolism and Chronic Inflammation: The Links Between Chronic Heart Failure and Comorbidities

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