Cardiac overexpression of constitutively active Galpha q causes angiotensin II type1 receptor activation, leading to progressive heart failure and ventricular arrhythmias in transgenic mice

• Published in: PloS one Vol. 9; no. 8; p. e106354
• Main Authors: Matsushita, Naoko, Kashihara, Toshihide, Shimojo, Hisashi, Suzuki, Satoshi, Nakada, Tsutomu, Takeishi, Yasuchika, Mende, Ulrike, Taira, Eiichi, Yamada, Mitsuhiko, Sanbe, Atsushi, Hirose, Masamichi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.08.2014; Public Library of Science (PLoS)
• Subjects: Action potential; Activation; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Angiotensin AT1 receptors; Angiotensin II; Angiotensins; Animal experimentation; Animals; Arrhythmia; Atrial Natriuretic Factor - metabolism; Blood pressure; Collagen; Collagen (type I); Collagen Type I - metabolism; Connective tissue growth factor; Contraction; Disease Models, Animal; EKG; Electrocardiography; Fibrosis; Gene expression; Gene Expression Regulation - drug effects; Genetic engineering; GTP-Binding Protein alpha Subunits, Gq-G11 - genetics; Heart; Heart diseases; Heart failure; Heart Failure - genetics; Heart Failure - physiopathology; Heart Failure - prevention & control; Hypertrophy; Imidazoles - administration & dosage; Kinases; Major histocompatibility complex; Medicine and Health Sciences; Mice; Mice, Transgenic; Myosin Heavy Chains - metabolism; Peptidyl-dipeptidase A; Proteins; Receptor mechanisms; Rodents; Tetrazoles - administration & dosage; Transgenic mice; Transient receptor potential proteins; Ventricle; Ventricular Premature Complexes - genetics; Ventricular Premature Complexes - physiopathology; Ventricular Premature Complexes - prevention & control; Rhode Island; United States > US; Japan

Transgenic mice with transient cardiac expression of constitutively active Galpha q (Gαq-TG) exhibt progressive heart failure and ventricular arrhythmias after the initiating stimulus of transfected constitutively active Gαq becomes undetectable. However, the mechanisms are still unknown. We examine...