LongShengZhi alleviated cardiac remodeling via upregulation microRNA-150-5p with matrix metalloproteinase 14 as the target

Abstract

Ethnopharmacological relevanceLongShengZhi capsule (LSZ), a traditional Chinese medicine, is used for treatment of patients with vascular diseases. LSZ reduced doxorubicin-induced heart failure by reducing production of reactive oxygen species and inhibiting inflammation and apoptosis. Aim of the studyThis study was to explore whether LSZ could alleviate cardiac remodeling via upregulation of microRNA (miR)-150-5p and the downstream target. Cardiac remodeling was induced by Ang II in vivo and in vitro. ResultsLSZ attenuated Ang II-induced cardiac hypertrophy and fibrosis in rats, and in primary cardiomyocytes (CMs) and primary cardiac fibroblasts (CFs). MiR-150-5p was downregulated in Ang II-induced rat heart, CMs and CFs, and these decreases were reserved by LSZ. In vivo overexpression of miR-150-5p by transfection of miR-150-5p agomiR protected Ang II-induced cardiac hypertrophy and fibrosis in rats. Meanwhile, its overexpression also reversed Ang II-induced upregulation of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) in rat hearts and primary CMs, as well as upregulation of collagen I, collagen III and transforming growth factor-β (TGF-β) in rat hearts and primary CFs. Matrix metalloproteinase 14 (MMP14) was validated as the target gene of miR-150-5p, which was overexpressed in Ang II-induced rat heart, rat primary CMs and primary CFs. Notably, overexpression of MMP14 induced cardiac remodeling, and reversed the protective role of miR-150-5p in downregulating Ang II-induced upregulation of hypertrophy and fibrosis markers in vitro. ConclusionCollectively, LSZ protects Ang II-induced cardiac dysfunction and remodeling via upregulation of miR-150-5p to target MMP14. Administration of LSZ, upregulation of miR-150-5p or targeting of MMP14 may be strategies for cardiac remodeling therapy.