Modulation of Vascular Smooth Muscle Cell Multiplication, Apoptosis, and Inflammatory Damage by miR-21 in Coronary Heart Disease.

Wei Liu,Yilin Li,Dongming Zhao

doi:10.1155/2021/6942699

Abstract

This study is aimed at exploring the role and potential molecular mechanism of microRNA-21 (miR-21) in coronary heart disease (CHD). RT-qPCR analysis was conducted to detect the expression of miR-21, Sprouty 1 (SPRY1), and connexin 43 (CX43). The protein expression of SPRY1 and CX43 was measured by western blot. ELISA was performed for measuring inflammatory factors, including intercellular adhesion molecule-1 (ICAM-1) and interleukin-1 beta (IL-1β). The target relationship between miR-21 and SPRY1 was determined by dual-luciferase reporter assay. Cell multiplication and apoptosis were detected using CCK-8 assay and flow cytometry analysis, respectively. Our results indicated that miR-21, CX43, and the level of inflammatory cytokines including ICAM-1 and IL-1β were upregulated, while SPRY1 was downregulated in blood samples from CHD patients compared with the controls. Besides, miR-21 directly targeted SRPY-1. miR-21 could suppress SPRY1 expression and enhance CX43 expression in VSMCs. Moreover, miR-21 accelerated cell multiplication and attenuated cell apoptosis in VSMCs. Collectively, these findings suggested that miR-21 could effectively elevate VSMC multiplication and repress apoptosis by targeting SPRY1 in CHD, providing a potential target for therapeutic strategy of CHD.

Highlights

Coronary heart disease (CHD) is a common cardiovascular disease usually resulted from atherosclerosis and has high mortality rate [1, 2]
The Levels of intercellular adhesion molecule-1 (ICAM-1) and IL-1β Were Elevated in CHD Patients
Comparing the contents of inflammatory factors in plasma from CHD patients and volunteers, we found that ICAM-1 and IL-1β were dramatically enhanced in CHD patients (Figures 2(a) and 2(b))

Summary

Introduction

Coronary heart disease (CHD) is a common cardiovascular disease usually resulted from atherosclerosis and has high mortality rate [1, 2]. There are multiple pathogenic factors of CHD, such as vascular stenosis, occlusion, myocardial ischemia, hypoxia, necrosis, inflammation, and cardiomyocyte apoptosis [3]. The treatment technology of CHD has made great progress, the prognosis of CHD patients is still worse due to the presence of comorbidities and the complexity of disease conditions [9, 10]. Accumulating evidence revealed that the aberrant proliferation of vascular smooth muscle cells (VSMCs) is a vital event in cardiovascular disease progression, including CHD [11, 12]. Inflammation and apoptosis are major causes of the initiation and progression of CHD, which have been regarded as the prognosis indicators for CHD patients after treatment [13, 14]. It is of significance to explore the action of miR-21 on VSMCs in CHD progression

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