The association between microRNA-21 and hypertension-induced cardiac remodeling

• Published in: PloS one Vol. 15; no. 2; p. e0226053
• Main Authors: Watanabe, Ken, Narumi, Taro, Watanabe, Tetsu, Otaki, Yoichiro, Takahashi, Tetsuya, Aono, Tomonori, Goto, Jun, Toshima, Taku, Sugai, Takayuki, Wanezaki, Masahiro, Kutsuzawa, Daisuke, Kato, Shigehiko, Tamura, Harutoshi, Nishiyama, Satoshi, Takahashi, Hiroki, Arimoto, Takanori, Shishido, Tetsuro, Watanabe, Masafumi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.02.2020; Public Library of Science (PLoS)
• Subjects: Activator protein 1; Aged; Aging; Angiotensin; Angiotensin II; Angiotensin II - pharmacology; Angiotensins; Animals; Animals, Newborn; Aorta; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Biology and Life Sciences; Blood pressure; Bone morphogenetic proteins; Cardiac function; Cardiology; Cardiomegaly - blood; Cardiomegaly - etiology; Cardiomegaly - pathology; Cardiomyocytes; Cardiomyopathy; Cardiovascular diseases; Cell death; Comparative analysis; Coronary artery disease; Deactivation; Development and progression; Disease Models, Animal; Diseases; Female; Fibrosis; Gene expression; Growth factors; Heart cells; Heart diseases; Heart failure; Heart hypertrophy; Humans; Hypertension; Hypertension - complications; Hypertrophy; Laboratory animals; Levels; Male; Medical schools; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; MicroRNA; MicroRNAs; MicroRNAs - genetics; Middle Aged; miRNA; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - metabolism; Neonates; Nephrology; Newborn infants; Older people; Organs; Public health; Public health movements; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Ribonucleic acid; RNA; RNA-Binding Proteins - metabolism; Scientific equipment industry; Signal transduction; Signal Transduction - drug effects; Signaling; Surgery; Transcription Factor AP-1 - metabolism; Transcription factors; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Transforming growth factors; United States; United States > US; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0226053

Hypertension is a major public health problem among the aging population worldwide. It causes cardiac remodeling, including hypertrophy and interstitial fibrosis, which leads to development of hypertensive heart disease (HHD). Although microRNA-21 (miR-21) is associated with fibrogenesis in multiple organs, its contribution to cardiac remodeling in hypertension is poorly understood. Circulating miR-21 level was higher in patients with HHD than that in the control subjects. It also positively correlated with serum myocardial fibrotic markers. MiR-21 expression levels were significantly upregulated in the mice hearts after angiotensin II (Ang II) infusion or transverse aortic constriction (TAC) compared with control mice. Expression level of programmed cell death 4 (PDCD4), a main target of miR-21, was significantly decreased in Ang II infused mice and TAC mice compared with control mice. Expression levels of transcriptional activator protein 1 (AP-1) and transforming growth factor-β1 (TGF-β1), which were downstream targets of PDCD4, were increased in Ang II infused mice and TAC mice compared with control mice. In vitro, mirVana-miR-21-specific inhibitor attenuated Ang II-induced PDCD4 downregulation and contributed to subsequent deactivation of AP-1/TGF-β1 signaling pathway in neonatal rat cardiomyocytes. Thus, suppression of miR-21 prevents hypertrophic stimulation-induced cardiac remodeling by regulating PDCD4, AP-1, and TGF-β1 signaling pathway.