Role of Rac1 GTPase Activation in Atrial Fibrillation

• Published in: Journal of the American College of Cardiology Vol. 50; no. 4; pp. 359 - 367
• Main Authors: Adam, Oliver, MD, Frost, Gregg, Custodis, Florian, MD, Sussman, Mark A., PhD, Schäfers, Hans-Joachim, MD, Böhm, Michael, MD, Laufs, Ulrich, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 24.07.2007; Elsevier Science; Elsevier Limited
• Subjects: Aged; Animals; Atrial Fibrillation - drug therapy; Atrial Fibrillation - enzymology; Atrial Fibrillation - pathology; Biological and medical sciences; Cardiac arrhythmia; Cardiac dysrhythmias; Cardiology; Cardiology. Vascular system; Cardiovascular; Cardiovascular disease; Collagen - metabolism; Coronary vessels; Disease Models, Animal; Enzyme Activation; Female; Fluorides; Fluorobenzenes - therapeutic use; GTP Phosphohydrolases - metabolism; Heart; Heart Atria - metabolism; Heart Atria - pathology; Heart rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypertension; Internal Medicine; Laboratory animals; Male; Medical sciences; Mice; Mice, Transgenic; Mortality; NADPH Oxidases - metabolism; Oxidative stress; Proteins; Pyrimidines - therapeutic use; rac1 GTP-Binding Protein - metabolism; Rodents; Rosuvastatin Calcium; Statins; Sulfonamides - therapeutic use; Surgery; Up-Regulation; United States > US; California; NADPH; wild-type mice; AF; left ventricle; nicotinamide adenine dinucleotide phosphate; ECG; LV; electrocardiography; atrial fibrillation; RacET; LA; TAC; transverse aortic constriction; sinus rhythm; left atrium; WT; transgenic mice with cardiac overexpression of Rac1 GTPase; SR; Arrhythmia; Enzyme; Triphosphoric monoester hydrolases; Atrial fibrillation; dGTPase; Cardiovascular disease; Esterases; Activation; Phlebology; Excitability disorder; Heart disease; Hydrolases; Circulatory system; Cardiology
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2007.03.041

Role of Rac1 GTPase Activation in Atrial Fibrillation Oliver Adam, Gregg Frost, Florian Custodis, Mark A. Sussman, Hans-Joachim Schäfers, Michael Böhm, Ulrich Laufs The signal transduction associated with atrial fibrillation (AF) is incompletely understood. Seventy-five percent of 16-month-old mice with cardiac-specific overexpression of constitutively active Rac1 but no wild-type or mice undergoing transaortic constriction showed AF. Treatment of transgenic mice with cardiac overexpression of Rac1 GTPase (RacET) with statins decreased cardiac Rac1 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and reduced the incidence of AF by 50%. Left atrial appendages of patients with AF showed increased fibrosis and up-regulation of NADPH oxidase and Rac1 activity. Therefore, chronic cardiac overexpression of Rac1 represents a mouse model for AF. Rac1 GTPase contributes to the pathogenesis of AF and identifies a novel treatment target.