Asiatic acid alleviates ischemic myocardial injury in mice by modulating mitophagy- and glycophagy-based energy metabolism

Qiu, Fan; Yuan, Yihao; Luo, Wei; Gong, Yanshan; Zhang, Zhongming; Liu, Zhongmin; Gao, Ling

doi:10.1038/s41401-021-00763-9

Cited by 33 publications

(16 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have shown that glycophagy is involved in cardiac glycogen homeostatic regulation in relation to fasting-induced metabolic stress in vivo ( 9 ). In vitro data evaluating shifts in Stbd1 levels with glycolysis activity are discrepant, possibly reflecting differences in cell origin—oncogenic versus developmental metabolic settings ( 69 , 84 ). Knockdown of Gaa in skeletal muscle cells (C2C12 myotubes) was associated with decreased glycolytic metabolic rate ( 77 ), further supporting the contention that glycophagy provides glucose substrate for glycolysis.…”

Section: Regulation Of Glycophagy and Lysosomal Glycogenolysismentioning

confidence: 99%

Glycogen-autophagy: Molecular machinery and cellular mechanisms of glycophagy

Koutsifeli¹,

Varma²,

Daniels³

et al. 2022

Journal of Biological Chemistry

View full text Add to dashboard Cite

Section: Regulation Of Glycophagy and Lysosomal Glycogenolysismentioning

confidence: 99%

Glycogen-autophagy: Molecular machinery and cellular mechanisms of glycophagy

Koutsifeli¹,

Varma²,

Daniels³

et al. 2022

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Asiatic acid (AA) is a pentacyclic triterpenoid derived from the traditional natural medicine, Centella asiatica, with anti-inflammatory, antioxidant, and antiapoptotic activities. AA has been found to improve the balance of energy metabolism in cardiomyocytes by activating mitophagy, thereby exerting a cardioprotective effect [ 146 ]. Treatment with different doses of AA increased cell viability, ATP levels, and the phosphocreatine/ATP ratio and improved cardiomyocyte energy metabolism.…”

Section: Natural Medicinal Plants and Active Ingredients In The Regul...mentioning

confidence: 99%

Protective Effect of Natural Medicinal Plants on Cardiomyocyte Injury in Heart Failure: Targeting the Dysregulation of Mitochondrial Homeostasis and Mitophagy

Wang

Liu

2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Heart failure occurs because of various cardiovascular pathologies, such as coronary artery disease or cardiorenal syndrome, eventually reaching end-stage disease. Various factors contribute to cardiac structural or functional changes that result in systolic or diastolic dysfunction. Several studies have confirmed that the key factor in heart failure progression is myocardial cell death, and mitophagy is the major mechanism regulating myocardial cell death in heart failure. The clinical mechanisms of heart failure are well understood in practice. However, the essential role of mitophagic regulation in heart failure has only recently received widespread attention. Receptor-mediated mitophagy is involved in various mitochondrial processes like oxidative stress injury, energy metabolism disorders, and calcium homeostasis, which are also the main causes of heart failure. Understanding of the diverse regulatory mechanisms in mitophagy and the complexity of its pathophysiology in heart failure remains incomplete. Related studies have found that various natural medicinal plants and active ingredients, such as flavonoids and saponins, can regulate mitophagy to a certain extent, improve myocardial function, and protect myocardial cells. This review comprehensively covers the relevant mechanisms of different types of mitophagy in regulating heart failure pathology and controlling mitochondrial adaptability to stress injury. Further, it explores the relationship between mitophagy and cardiac ejection dysfunction. Natural medicinal plant-targeted regulation strategies and scientific evidence on mitophagy were provided to elucidate current and potential strategies to apply mitophagy-targeted therapy for heart failure.

show abstract

“…Immunofluorescent staining was performed in the heart tissue sections as previously described [24]. For wheat germ agglutinin (WGA) staining, the sections were stained using an FITC-labeled WGA dye (Sigma-Aldrich).…”

Section: Immunofluorescencementioning

confidence: 99%

Exosomes secreted by endothelial cells derived from human induced pluripotent stem cells protect heart from myocardial infarction by modulating cardiomyocyte calcium homeostasis

Wang

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Human induced pluripotent stem cell–derived endothelial cells (hiPSC-ECs) exhibit potential in repairing the injured heart after myocardial infarction (MI) by promoting neovascularization and cardiomyocyte survival. However, because of the low cellular retention and poor engraftment efficacy, cell therapy treatment of MI is in part mediated by exosomes secreted from the transplanted cells. We investigated whether exosomes secreted from hiPSC-ECs could become a promising acellular approach to repairing the infarcted heart after MI, and elucidated the underlying protective mechanism. Methods: hiPSC-ECs were differentiated and exosomes were isolated in vitro. Then, hiPSC-EC exosomes were delivered by intramyocardial injection in a murine MI model in vivo. Echocardiography, combined with hemodynamic measurement, histological examination, Ca2+ transient and cell shortening assessment, and western blot, was used to determine protective effects of hiPSC-EC exosomes on the infarcted heart. Furthermore, microRNA sequencing, luciferase activity assay, and microRNA gain–loss function experiments were performed to investigate the enriched microRNA and its role in exosome-mediated effects. Results: In vitro assessments demonstrated that hiPSC-EC exosomes could be taken up by cardiomyocytes and that they possess the capability to protect cardiomyocytes from oxygen–glucose deprivation injury by enhancing Ca2+ transients, increasing ATP content, and promoting cell survival. Congruously, hiPSC-EC exosomes administration in vivo not only improved myocardial contractile function but also attenuated the harmful left ventricular remodeling after MI. Mechanistically, hiPSC-EC exosomes notably rescued the protein expression and function of sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA-2a) and ryanodine receptor 2 (RyR-2) to maintain intracellular Ca2+ homeostasis and increase cardiomyocyte contraction after MI. microRNA sequencing determined that miR-100-5p was the most abundant microRNA in exosomes, and miR-100-5p could target protein phosphatase 1β (PP-1β) to enhance the phosphorylation level of phospholamban (PLB) at Ser16 and subsequent SERCA activity, which contributes to the hiPSC-EC exosome–exerted cytoprotective effects on maintaining intracellular Ca2+ homeostasis and promoting cardiomyocyte survival. Conclusion: hiPSC-EC exosomes maintain cardiomyocyte Ca2+ homeostasis to improve myocardial recovery after MI, which may provide an acellular therapeutic option for myocardial injury. Keywords: hiPSC-ECs, exosomes, Ca2+ homeostasis, miR-100-5p

show abstract

Asiatic acid alleviates ischemic myocardial injury in mice by modulating mitophagy- and glycophagy-based energy metabolism

Cited by 33 publications

References 49 publications

Glycogen-autophagy: Molecular machinery and cellular mechanisms of glycophagy

Glycogen-autophagy: Molecular machinery and cellular mechanisms of glycophagy

Protective Effect of Natural Medicinal Plants on Cardiomyocyte Injury in Heart Failure: Targeting the Dysregulation of Mitochondrial Homeostasis and Mitophagy

Exosomes secreted by endothelial cells derived from human induced pluripotent stem cells protect heart from myocardial infarction by modulating cardiomyocyte calcium homeostasis

Contact Info

Product

Resources

About