Basal autophagy is tightly regulated by transcriptional and epigenetic factors to maintain cellular homeostasis. Dysregulation of cardiac autophagy is associated with heart diseases, including cardiac hypertrophy, but the mechanism governing cardiac autophagy is rarely identified. To analyze the in vivo function of miR-199a in cardiac autophagy and cardiac hypertrophy, we generated cardiac-specific miR-199a transgenic mice and showed that overexpression of miR-199a was sufficient to inhibit cardiomyocyte autophagy and induce cardiac hypertrophy in vivo. miR-199a impaired cardiomyocyte autophagy in a cell-autonomous manner by targeting glycogen synthase kinase 3β (GSK3β)/mammalian target of rapamycin (mTOR) complex signaling. Overexpression of autophagy related gene 5 (Atg5) attenuated the hypertrophic effects of miR-199a overexpression on cardiomyocytes, and activation of autophagy using rapamycin was sufficient to restore cardiac autophagy and decrease cardiac hypertrophy in miR-199a transgenic mice. These results reveal a novel role of miR-199a as a key regulator of cardiac autophagy, suggesting that targeting miRNAs controlling autophagy as a potential therapeutic strategy for cardiac disease.
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http://dx.doi.org/10.1038/cdd.2015.95 | DOI Listing |
World J Cardiol
January 2025
Institute of Cardiovascular Diseases & Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan Province, China.
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy. It is one of the chief causes of sudden cardiac death in younger people and athletes. Molecular-genetic studies have confirmed that the vast majority of HCM is caused by mutations in genes encoding sarcomere proteins.
View Article and Find Full Text PDFClin Epigenetics
January 2025
Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
Diabetic cardiomyopathy (DbCM), a significant chronic complication of diabetes, manifests as myocardial hypertrophy, fibrosis, and other pathological alterations that substantially impact cardiac function and elevate the risk of cardiovascular diseases and patient mortality. Myocardial energy metabolism disturbances in DbCM, encompassing glucose, fatty acid, ketone body and lactate metabolism, are crucial factors that contribute to the progression of DbCM. In recent years, novel protein post-translational modifications (PTMs) such as lactylation, β-hydroxybutyrylation, and succinylation have been demonstrated to be intimately associated with the myocardial energy metabolism process, and in conjunction with acetylation, they participate in the regulation of protein activity and gene expression activity in cardiomyocytes.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany.
Pathological cardiac remodeling is a maladaptive response that leads to changes in the size, structure, and function of the heart. These changes occur due to an acute or chronic stress on the heart and involve a complex interplay of hemodynamic, neurohormonal and molecular factors. As a critical regulator of cell growth, protein synthesis and autophagy mechanistic target of rapamycin complex 1 (mTORC1) is an important mediator of pathological cardiac remodeling.
View Article and Find Full Text PDFEur J Prev Cardiol
January 2025
St Vincent's Institute of Medical Research, 9 Princes St Fitzroy VIC 3065 Australia.
Aim: To define the association between severe coronary artery disease and widespread atherosclerosis in younger individuals.
Methods: Individuals aged 1-50 years with sudden cardiac death (SCD) from 2019-23, autopsy-proven to be due to coronary artery disease, were identified using the state-wide EndUCD registry. Presence of extra-coronary atherosclerosis greater than modified American Heart Association class III was assessed in 5 arterial beds (intra-cerebral vessels, aorta, carotid, renal and femoral arteries).
Front Biosci (Landmark Ed)
January 2025
Department of Biomedical Sciences, Grand Valley State University, Allendale, MI 49401, USA.
Background: Diabetes mellitus is associated with morphological and functional impairment of the heart primarily due to lipid toxicity caused by increased fatty acid metabolism. Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) have been implicated in the metabolism of fatty acids in the liver and skeletal muscles. However, their role in the heart in diabetes remains unclear.
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