Role for MicroRNA-21 in Atrial Profibrillatory Fibrotic Remodeling Associated With Experimental Postinfarction Heart Failure

• DOI: 10.1161/circep.112.973214
• Publication Date: 2012-08-27T00:13:12Z
• Authors: Sophie Cardin; Eduard Guasch; Xiaobin Luo; Patrice Naud; Khaï Le Quang; YanFen Shi; Jean-Claude Tardif; Philippe Comtois; Stanley Nattel
• Keywords: Ventricular remodeling

Background— Atrial tissue fibrosis is often an important component of the atrial fibrillation (AF) substrate. Small noncoding microRNAs are mediators in many cardiac remodeling paradigms. MicroRNA-21 (miR-21) has been suggested to be ventricular fibrotic by downregulating Sprouty-1, a protein that suppresses fibroblast proliferation. The present study examined potential role miR-21 AF substrate resulting from experimental heart failure after myocardial infarction (MI). Methods and Results— Large MIs (based on echocardiographic left wall motion score index) were created anterior descending coronary artery ligation rats. Changes induced MI versus sham controls first characterized with echocardiography, histology, biochemistry, vivo electrophysiology. Additional rats then randomized receive anti–miR-21 (KD21) or scrambled control sequence (Scr21) injections into myocardium. Progressive enlargement, hypocontractility, dilation, fibrosis, refractoriness prolongation, promotion occurred controls. tissues showed upregulation miR-21, along dysregulation target genes collagen-1, collagen-3. KD21 treatment reduced expression levels values rats, decreased duration 417 (69–1595; median [Q1–Q3]) seconds 3 (2–16) (8 weeks MI; P <0.05), fibrous content 14.4±1.8% (mean±SEM) 4.9±1.2% <0.05) Scr21 Conclusions— MI-induced leads AF-promoting knockdown promotion, implicating as signaling molecule for pointing molecular interventions designed prevent AF.