Exosomal microRNA-29a mediates cardiac dysfunction and mitochondrial inactivity in obesity-related cardiomyopathy

• Published in: Endocrine Vol. 63; no. 3; pp. 480 - 488
• Main Authors: Li, Fengqin, Zhang, Kuikui, Xu, Ting, Du, Wenjuan, Yu, Bo, Liu, Youbin, Nie, Honggang
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2019; Springer Nature B.V
• Subjects: Animals; Cardiac function; Cardiomyocytes; Cardiomyopathies - blood; Cardiomyopathies - etiology; Cardiomyopathies - physiopathology; Cardiomyopathy; Diabetes; Diet, High-Fat - adverse effects; Electron transport chain; Endocrinology; Exosomes; Exosomes - metabolism; High fat diet; Human subjects; Humanities and Social Sciences; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Mice, Inbred C57BL; MicroRNAs; MicroRNAs - metabolism; Middle Aged; miRNA; Mitochondria; Mitochondria, Heart - metabolism; multidisciplinary; NADH-ubiquinone oxidoreductase; Natriuretic Peptide, Brain - blood; Obesity; Obesity - blood; Obesity - complications; Obesity - physiopathology; Original Article; Oxygen consumption; Peptide Fragments - blood; Science; Stroke Volume; Structure-function relationships; Heart; Obesity; Mitochondria; Exosome; MicroRNA-29a
• ISSN: 1355-008X; 1559-0100; 1559-0100
• DOI: 10.1007/s12020-018-1753-7

Purpose Present study aims to explore the pathophysiological role of microRNA (miR)-29a in the process of obesity-related cardiomyopathy in human subjects and mice. Methods The expression level of circulating exosomal miR-29a was measured in 37 lean and 30 obese human subjects, and correlated with cardiac parameters. The effects of miR-29a on mitochondrial activity and cardiac function were investigated by treatment of miR-29a sponge in primary mouse cardiomyocytes and diet-induced obesity-related cardiomyopathy in mice. Results The increased circulating miR-29a level was closely associated with impaired human cardiac function, including ejection fraction ( r  = −0.2663, p  < 0.05) and NT-proBNP levels ( r  = 0.4270, p  < 0.001). Exosomes from obese human plasma mediated cardiomyocyte mitochondrial inactivity, but pre-treatment with miR-29a sponge attenuated the exosomal miR-29a-induced reduction of ATP production ( p  < 0.001), basal oxygen consumption ( p  < 0.01) and mitochondrial complex I activity ( p  < 0.01). In vivo mouse study, high fat diet damaged cardiac function, normal structure, and mitochondrial activity, whereas miR-29a sponge improved the cardiac status. Conclusions Present study uncovered the correlation between circulating miR-29a and cardiac parameters in human subjects, and provided solid evidence of the therapeutic application of miR-29a sponge in combating obesity-mediated cardiac dysfunction.