MicroRNA-327 regulates cardiac hypertrophy and fibrosis induced by pressure overload

Abstract

MicroRNA (miRNA/miR) dysregulation has been reported to be fundamental in the development and progression of cardiac hypertrophy and fibrosis. In the present study, miR-327 levels in fibroblasts were increased in response to cardiac hypertrophy induced by transverse aortic constriction with prominent cardiac fibrosis, particularly when compared with the levels in unstressed cardiomyocytes. In neonatal rat cardiac fibroblasts, induced expression of miR-327 upregulated fibrosis-associated gene expression and activated angiotensin II-induced differentiation into myofibroblasts, as assessed via α-smooth muscle actin staining. By contrast, miR-327 knockdown mitigated angiotensin II-induced differentiation. Cardiac fibroblast proliferation was not affected under either condition. In a mouse model subjected to transverse aortic constriction, miR-327 knockdown through tail-vein injection reduced the development of cardiac fibrosis and ventricular dysfunction. miR-327 was demonstrated to target integrin β3 and diminish the activation of cardiac fibroblasts. Thus, the present study supports the use of miR-327 as a therapeutic target in the reduction of cardiac fibrosis.

New Insights into the Functions of MicroRNAs in Cardiac Fibrosis: From Mechanisms to Therapeutic Strategies

“…In vivo silencing of miR-125b could rescue Ang-II-induced cardiac fibrosis [ 54 ]. Moreover, overexpression of miR-327 promoted Ang-II-induced differentiation of cardiac fibroblasts into myofibroblasts [ 65 ], while let-7i miRNAs exhibited opposite effects [ 86 ].…”

Activating transcription factor 3 inhibits angiotensin II‑induced cardiomyocyte viability and fibrosis by activating the transcription of cysteine‑rich angiogenic protein 61

“…During cardiac hypertrophy, the regulation of cardiac fibroblasts by Ang II and other factors results in excessive proliferation and the production of excessive quantities of fibrin, which leads to cardiac fibrosis and can further aggravate cardiac hypertrophy (26)(27)(28). Therefore, inhibition of the proliferation and fibrosis of cardiac fibroblasts may serve as a viable strategy for treating cardiac hypertrophy.…”

Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway

“…In parallel, Ji et al (Ji et al, 2018) reported that the miR-327 expression was the highest in fibrotic heart tissue induced by transverse aortic constriction (TAC) in mice, and downregulation of miR-327 inhibited cardiac hypertrophy and fibrosis by targeting integrin β3(ITGB3). In addition, some studies reported that excessive ROS can activate MMPs, which play an important role in LV remodeling (Hori and Nishida, 2009;Baghirova et al, 2016).…”