沉默 TLR4 通过下调 NLRP3-TGF- 抑制自发性高血压大鼠心房纤维化和心房颤动易感性。

Silencing of TLR4 Inhibits Atrial Fibrosis and Susceptibility to Atrial Fibrillation via Downregulation of NLRP3-TGF- in Spontaneously Hypertensive Rats.

机构信息

Department of Geriatrics Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

Internal Medicine-Cardiovascular Department, Jiangbin Hospital, Nanning 530021, China.

出版信息

Dis Markers. 2022 Jul 11;2022:2466150. doi: 10.1155/2022/2466150. eCollection 2022.

INTRODUCTION

This study was aimed at exploring whether silencing of TLR4 could inhibit atrial fibrosis and susceptibility to atrial fibrillation (AF) by regulating NLRP3-TGF- in hypertensive rats.

METHODS

Spontaneously hypertensive rats (SHRs) were transfected with either a virus containing TLR4-shRNA to downregulate TLR4 or an empty virus (vehicle) at the age of 14 weeks. Fibrosis of left atrium and susceptibility to AF were detected, and expression of NLRP3-TGF- in left atrial tissue at 22 weeks of age was measured. Primary cardiac fibroblasts were transfected with TLR4-shRNA or scrambled vehicle and stimulated with angiotensin (Ang) II. Proliferation of cardiac fibroblasts and expression of NLRP3-TGF- were detected.

RESULTS

Silencing of TLR4 reduced left atrial fibrosis and susceptibility to AF in SHRs and downregulated expression of NLRP3, TGF-, and collagen I. In vitro, TLR4 silencing reduced proliferation of cardiac fibroblasts induced by Ang II as well as expression of NLRP3, TGF-, and collagen I.

CONCLUSION

Silencing of TLR4 can downregulate NLRP3-TGF- to reduce atrial fibrosis and susceptibility to AF in SHRs.

简介

本研究旨在探讨沉默 TLR4 是否可以通过调节 NLRP3-TGF- 来抑制高血压大鼠的心房纤维化和心房颤动（AF）易感性。

方法

在 14 周龄时，将含有 TLR4-shRNA 的病毒或空病毒（载体）转染自发性高血压大鼠（SHR）以下调 TLR4。在 22 周龄时检测左心房纤维化和 AF 易感性，并测量左心房组织中 NLRP3-TGF- 的表达。将 TLR4-shRNA 或乱序载体转染原代心肌成纤维细胞，并用血管紧张素（Ang）II 刺激。检测心肌成纤维细胞的增殖和 NLRP3-TGF- 的表达。