Endothelial MicroRNA-483-3p Is Hypertension-Protective.

Fenqing Shang,Liang Bai,Baochang Lai,Xuan Guo,Chen Wang,Ergang Wen,Jie Gao,Yueer Chen,Qi Yu

doi:10.1155/2022/3698219

Abstract

Hypertension is a high-risk factor for developing coronary heart disease and stroke. Endothelial dysfunction and arterial remodeling can lead to increased vascular wall thickness and arterial stiffness. Previous studies showed that microRNA-483 (miR-483) enhances endothelial cell (EC) function. Here, we investigated the protective role of miR-483 in hypertension. Data collected from two patient cohorts showed that the serum miR-483-3p level was associated with the progression of hypertension and positively correlated with vascular function. In cultured ECs, miR-483 targets a number of endothelial dysfunction-related genes, such as transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), angiotensin-converting enzyme 1 (ACE1), and endothelin-1 (ET-1). Overexpression of miR-483-3p in ECs inhibited Ang II-induced endothelial dysfunction, revealed by the decreased expression of TGF-β, CTGF, ACE1, and ET-1. Furthermore, miR-483-3p secreted from ECs was taken up by smooth muscle cells (SMCs) via the exosome pathway, which also decreased these genes in SMCs. Additionally, telmisartan could increase the aortic and serum levels of miR-483-3p in hypertension patients and spontaneous hypertension rats (SHR). These findings suggest that miR-483-3p exerts a protective effect on EC function during the onset of hypertension and thus may be considered a potential therapeutic target for hypertension-related cardiovascular diseases.

Highlights

Hypertension, a major contributor for developing cardiac and peripheral vascular diseases, is considered an important worldwide problem of public health [1, 2]
We found that the serum miR-483-3p level was increased in patients with newly diagnosed hypertension, while it decreased in patients with chronic hypertension
Serum levels of miR-483-3p are upregulated in patients with first-diagnosed hypertension, while they are downregulated in patients with long-term hypertension

Summary

Introduction

Hypertension, a major contributor for developing cardiac and peripheral vascular diseases, is considered an important worldwide problem of public health [1, 2]. The key features of hypertension include endothelial dysfunction and arterial remodeling, which lead to increased vascular wall thickness and arterial stiffness [3,4,5]. The nitrogen oxide (NO)/ endothelin-1 (ET-1) coefficient is a criterion for the risk of developing hypertension [6]. As the pathophysiological causes of hypertension are multifaceted, endothelial dysfunction can contribute to the imbalance between NO and ET-1 [4]. The cellular cross talk between endothelial cells (ECs) and SMCs is crucial for blood vessel remodeling under hypertension [8]. The cellular and molecular basis involved in their vasculopathic effects is little known

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Conclusion