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

Abstract

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