MicroRNA-19 upregulation attenuates cardiac fibrosis via targeting connective tissue growth factor

In the case of heart failure, electrical conduction, energy metabolism and cardiac contractility are disrupted, all disabling the heart to fulfill its circulatory roles. ^, Heart failure is preceded by adverse left ventricle (LV) remodeling, as manifested by hypertrophy or dilatation. ^, Cardiac fibrosis is a key driver of chronic heart failure. ^, In addition, excessive cardiac fibrosis causes large infarction that impair cardiac function. ^, Cardiac fibrosis is characterized by the accumulation of extracellular matrix in the myocardium. Cardiac fibroblasts (CFs) are major participators in fibrosis, ^,

but their mechanisms remain poorly understood.

MicroRNAs (miRs), a group of small and non-coding RNAs, can bind to the complementary 3’-untranslated region to inhibit messenger RNA (mRNA) translation, thus negatively regulating gene expression at the post-transcriptional level.

Many miRNAs play pathogenic roles in processes of heart failure, such as apoptosis, remodeling, hypoxia, or hypertrophy. ^, In aging-associated heart failure, the expression level of miR-19 decreased, but in heart failure-resistant mice, this level increased.

The effects of miR-19 on cardiac fibrosis and associated mechanisms are still unclear.

Connective tissue growth factor (CTGF) is a cysteine-rich matricellular protein involved in various biological processes, such as cell adhesion, angiogenesis, proliferation and differentiation, as well as tissue fibrosis.

CTGF monoclonal antibody can repair the infarcted tissue and attenuate LV hypertrophy and fibrosis to enhance survival and LV function. MiR-19 can modulate the expression of extracellular matrix proteins and CTGF in cardiomyocytes. The purpose of this study was to explore the cardioprotective effects of miR-19 in rats with MI-induced heart failure and associated regulatory mechanisms.