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

Qinghua Huang; Jiangbo Ma; Hui Wu; Jieru Zhou; Lei Jiang; Xianming Fei

doi:10.31083/j.fbl2807155

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

Front Biosci (Landmark Ed). 2023 Jul 28;28(7):155. doi: 10.31083/j.fbl2807155.

Authors

Qinghua Huang^{1

2}, Jiangbo Ma¹, Hui Wu¹, Jieru Zhou³, Lei Jiang⁴, Xianming Fei⁴

Affiliations

¹ Geriatric Medicine Center, Department of Endocrinology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310014 Hangzhou, Zhejiang, China.
² Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, 310014 Hangzhou, Zhejiang, China.
³ Jinzhou Medical University, 121001 Jinzhou, Liaoning, China.
⁴ Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310014 Hangzhou, Zhejiang, China.

PMID: 37525903
DOI: 10.31083/j.fbl2807155

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.

Keywords: BMSCs; cGMP/PKG pathway; cardiomyocytes apoptosis; diabetic cardiomyopathy; myocardial fibrosis; phosphodiesterase-5.

Abstract

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