Role of Caveolin-1 in Atrial Fibrillation as an Anti-Fibrotic Signaling Molecule in Human Atrial Fibroblasts

• Published in: PloS one Vol. 9; no. 1; p. e85144
• Main Authors: Yi, Shao-lei, Liu, Xiao-jun, Zhong, Jing-quan, Zhang, Yun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.01.2014; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Analysis; Arrhythmia; Atrial fibrillation; Atrial Fibrillation - metabolism; Atrial Fibrillation - pathology; Atrial Remodeling - drug effects; Atrium; Biology; Biopsy; Bone morphogenetic proteins; Cardiac arrhythmia; Cardiology; Cardiomyocytes; Cardiomyopathy; Cardiovascular disease; Caveolae; Caveolin; Caveolin 1 - chemistry; Caveolin 1 - deficiency; Caveolin 1 - genetics; Caveolin 1 - metabolism; Caveolin-1; Cell culture; Collagen; Collagen - biosynthesis; Collagens; Down-Regulation - drug effects; Education; Endothelium; Female; Fibrillation; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Fibrosis; Gelatinase A; Gene Knockdown Techniques; Growth factors; Heart; Heart Atria - pathology; Heart diseases; Histopathology; Hospitals; Humans; Hypertension; Hypotheses; Kinases; Laboratories; Male; Medicine; Middle Aged; Organelles; Peptide Fragments - pharmacology; Peptides; Protein Structure, Tertiary; Public health; RNA, Small Interfering - genetics; Rodents; Signal transduction; Signal Transduction - drug effects; Signaling; Sinus; siRNA; Smad protein; Smad Proteins - metabolism; Studies; Transforming growth factor; Transforming Growth Factor beta1 - pharmacology; Transforming growth factor-b1; Transforming growth factors; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0085144

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the general population; yet, the precise mechanisms resulting in AF are not fully understood. Caveolin-1 (Cav-1), the principal structural component of caveolae organelles in cardiac fibroblasts, is involved in several cardiovascular conditions; however, the study on its function in atrium, in particular, in AF, is still lacking. This report examines the hypothesis that Cav-1 confers an anti-AF effect by mediating atrial structural remodeling through its anti-fibrotic action. We evaluated the expression of Cav-1, transforming growth factor-β1 (TGF-β1), and fibrosis in atrial specimens of 13 patients with AF and 10 subjects with sinus rhythm, and found that the expression of Cav-1 was significantly downregulated, whereas TGF-β1 level, collagens I/III contents and atrial fibrosis were markedly increased, in AF. Western blot analysis demonstrated that treatment of human atrial fibroblasts (HAFs) with TGF-β1 resulted in a concentration- and time-dependent repression of Cav-1. Downregulation of Cav-1 with siRNA increased the TGF-β1-induced activation of Smad signal pathway and collagens production in HAFs. Furthermore, incubation of HAFs with the peptides derived from Cav-1 to achieve Cav-1 gain-of-function abolished the TGF-β1-induced production of collagens I/III and decreases of MMP-2/-9 expression. Therefore it was concluded that Cav-1 is an important anti-AF signaling mediator by conferring its anti-fibrotic effects in atrium.