miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN

• Published in: Molecular therapy. Nucleic acids Vol. 12; pp. 254 - 266
• Main Authors: Nie, Xiang, Fan, Jiahui, Li, Huaping, Yin, Zhongwei, Zhao, Yanru, Dai, Beibei, Dong, Nianguo, Chen, Chen, Wang, Dao Wen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.09.2018; Elsevier Limited; American Society of Gene & Cell Therapy; Elsevier
• Subjects: Aorta; Biomarkers; Cardiac function; cardiac hypertrophy; Cardiomyocytes; Cardiovascular disease; Congestive heart failure; Echocardiography; exosome; Exosomes; Fibroblasts; Fibrosis; Heart failure; Hypertrophy; MicroRNAs; miR-217; miRNA; Plasma; Pressure; Protein synthesis; Proteins; PTEN; PTEN protein; Structure-function relationships; Studies; Therapeutic applications; Thorax; China; PTEN; cardiac hypertrophy; miR-217; exosome
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2018.05.013

Previously, we found that the miR-217 expression level was increased in hearts from chronic heart failure (CHF) patients by using miRNA profile analysis. This study aimed to explore the role of miR-217 in cardiac dysfunction. Heart tissue samples from CHF patients were used to detect miR-217 expression levels. A type 9 recombinant adeno-associated virus (rAAV9) was employed to manipulate miR-217 expression in mice with thoracic aortic constriction (TAC)-induced cardiac dysfunction. Cardiac structure and function were measured by echocardiography and invasive pressure-volume analysis. The expression levels of miR-217 were increased in hearts from both CHF patients and TAC mice. Overexpression of miR-217 in vivo aggravated pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction, whereas miR-217-TUD-mediated downregulation of miR-217 reversed these effects. PTEN was predicted and validated as a direct target of miR-217, and re-expression of PTEN attenuated miR-217-mediated cardiac hypertrophy and cardiac dysfunction. Importantly, cardiomyocyte-derived miR-217-containing exosomes enhanced proliferation of fibroblasts in vitro. All of these findings show that miR-217 participates in cardiac hypertrophy and cardiac fibrosis processes through regulating PTEN, which suggests a promising therapeutic target for CHF.