Yixintongmai Inhibits Proliferation and Migration and Promotes Apoptosis of Vascular Smooth Muscle Cells Cultured with High Glucose.

Jingjing Guo,Di Zhao,Pingshuan Dong,Gourav Dey

doi:10.1155/2021/6583086

Abstract

Objective This study was designed to evaluate the effects of yixintongmai on proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) cultured with high glucose. Methods VSMCs of the thoracic aorta from 5- to 8-week-old male Sprague-Dawley rats were cultured with normal (4.5 mM) or high (25 mM) glucose, respectively. The concentration of yixintongmai powder at 360 μg/ml was chosen according to pre-experimental results. Results Yixintongmai inhibited the proliferation of VSMCs (CCK-8 assay: 0.75 ± 0.04 versus 0.98 ± 0.09 OD, P < 0.001; cell counting: 37533 ± 1861 versus 56009 ± 3779 cells/well, P < 0.001) and the expression of proliferating cell nuclear antigen (0.74 ± 0.08 fold, P < 0.001) as compared with high glucose (HG). Yixintongmai inhibited the migration of VSMCs (transwell assay: 146 ± 16 versus 265 ± 62 cells; P < 0.001), scratch wound assay (0.17 ± 0.01 fold, P < 0.001), and the expression of matrix metalloproteinases-9 (0.87 ± 0.03 fold, P < 0.001) as compared with HG. Yixintongmai decreased mitochondrial membrane potentials (0.36 ± 0.12 fold, P < 0.001) and promoted early (2.11 ± 0.20 fold, P < 0.01) and late (2.11 ± 0.28 fold, P < 0.01) apoptosis of VSMCs as compared with HG. Yixintongmai inhibited the expression of B-cell lymphoma 2 (0.83 ± 0.07 fold, P < 0.01) and stimulated the activity of cleaved-capase-3/caspase-3 (2.00 ± 0.12 fold, P < 0.05) as compared with HG. Yixintongmai inhibited reactive oxygen species generation (0.46 ± 0.03 fold, P < 0.01) and the expression of NADPH oxidase-1 (0.84 ± 0.04 fold, P < 0.001), nuclear factor-kappa B (NF-κB) p65 (0.71 ± 0.07 fold, P < 0.001), phosphorylated NF-κB p65 (0.39 ± 0.02 fold, P < 0.0001), and inhibited nuclear translocation of NF-κB p65 (0.87 ± 0.03 fold, P < 0.001) in VSMCs as compared with HG. Conclusions Yixintongmai inhibits the proliferation and migration and promotes the apoptosis of VSMCs cultured with HG, which suggests the potential anti-atherosclerotic effects of this traditional Chinese medicine.

Highlights

Cardiovascular complications are the major cause of death in patients with type 2 diabetes mellitus (T2DM). e role of hyperglycemia and hyperinsulinemia in the pathogenesis of diabetic atherosclerosis is still largely unclear [1]
Yixintongmai Inhibits the Proliferation of vascular smooth muscle cells (VSMCs) and the Expression of proliferating cell nuclear antigen (PCNA) of VSMCs Cultured with High Glucose
Yixintongmai Inhibits the Migration of VSMCs and the Expression of matrix metalloprotein 9 (MMP-9) of VSMCs Cultured with High Glucose

Summary

Introduction

Cardiovascular complications are the major cause of death in patients with type 2 diabetes mellitus (T2DM). e role of hyperglycemia and hyperinsulinemia in the pathogenesis of diabetic atherosclerosis is still largely unclear [1]. Hyperglycemia-induced overproduction of reactive oxygen species (ROS) may be the key molecular mechanisms for diabetes mediated vascular damage [2]. NF-κB activation in VSMCs represents a key mechanism for the accelerated vascular disease observed in diabetes and is a pivotal stimulator for VSMCs dedifferentiation, proliferation, and migration [3]. Several studies demonstrated that yixintongmai could inhibit restenosis after coronary angioplasty in patients with coronary artery diseases and T2DM [5]. Milkvetch root [6] and danshen root [7], the specific ingredient of yixintongmai, inhibited the progress of atherosclerosis through affecting the proliferation, migration, and apoptosis. We determined the effects of yixintongmai on ROS generation and the expression of NF-κB of VSMCs cultured with high glucose

Methods

Results

Discussion