Atrial fibrillation induces myocardial fibrosis through angiotensin II type 1 receptor-specific Arkadia-mediated downregulation of Smad7.

ABSTRACT:

Rationale

Tachycardia-induced atrial fibrosis is a hallmark of structural remodeling of atrial fibrillation (AF). The molecular mechanisms underlying the AF-induced atrial fibrosis remain unclear.

Objective

To determine the role of angiotensin II (Ang II)/Ang II type 1 (AT(1)) receptor-coupled transforming growth factor (TGF)-β(1)/Smad signaling pathway in the AF-induced atrial fibrosis.

Methods and results

Rapid atrial pacing (1000 ppm) was applied to the left atrium of rabbit heart to induce atrial fibrillation and fibrosis. Quantitative PCR and Western blot analysis revealed that rapid atrial pacing caused a marked increase in the expression of Ang II, TGF-β(1), phosphorylated Smad2/3 (P-Smad2/3), Arkadia, and hydroxyproline synthesis. However, the expression of Sm

SUBMITTER: He X 

PROVIDER: S-EPMC3035429 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature