PDE-5-Inhibited BMSCs Alleviate High Glucose-Induced Myocardial Fibrosis and Cardiomyocyte Apoptosis by Activating the cGMP/PKG Pathway.

ABSTRACT

BACKGROUND: Phosphodiesterase-5 (PDE-5) inhibitors have been found to play an important cardio-protective role. This study aimed to clarify the inhibitory effects of PDE-5-silenced bone marrow mesenchymal stem cells (BMSCs) on high glucose-induced myocardial fibrosis and cardiomyocyte apoptosis. METHODS: Cardiomyocytes and fibroblasts of neonatal rats were treated with high glucose (HG), and co-cultured with PDE-5-overexpressed or -knocked down BMSCs. The viability and apoptosis as well as the levels of cytokines, Cardiac troponin I and Vimentin of cardiomyocytes and fibroblasts were studied. The expressions of PDE-5, cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG), in both cells were evaluated. RESULTS: BMSCs that silenced PDE-5 facilitated the viability of cardiomyocytes, decreased the viability of fibroblasts, and inhibited the apoptosis of cardiomyocytes and fibroblasts. The contents of collagen-I, collagen-III, tissue inhibitor of metalloproteinase (TIMP)-1 and Dermin in fibroblasts were decreased by the PDE-5 inhibitor, but the levels of matrix metalloproteinase (MMP)-1 in fibroblasts and troponin-I in cardiomyocytes were increased by the PDE-5 inhibitor. PDE-5 inhibitor also suppressed the expression of PDE-5 but up-regulated cGMP and PKG expression in cardiomyocytes and fibroblasts. CONCLUSIONS: PDE-5-inhibited BMSCs can decrease HG-induced myocardial fibrosis and cardiomyocyte apoptosis by activating the cGMP/PKG pathway, and may play a role in the prevention and treatment of diabetic cardiomyopathy.