title: Hyperthermia treatment prevents angiotensin II-mediated atrial fibrosis and fibrillation via induction of heat-shock protein 72.
abstract: We tested the hypothesis that atrial fibrosis and atrial fibrillation (AF) evoked by angiotensin II (AII) could be prevented by the induction of heat-shock protein 72 (HSP72) by hyperthermia (HT). In cultured atrial fibroblasts isolated from male Sprague-Dawley rats, HT (42 degrees C) was applied for 30 min. AII (100 nmol/L) was added to the medium 8 h later. HT induced the expression of HSP72, which was associated with the attenuation of AII-induced extracellular signal-regulated kinase (ERK1/ERK2) phosphorylation, alpha-smooth muscle actin (alpha-SMA) expression, transforming growth factor-beta(1) secretion, collagen synthesis, and expression of collagen type I and tissue inhibitor of metalloproteinases-1. A small interfering RNA targeting HSP72 abolished these anti-fibrotic effects of HT. In male Sprague-Dawley rats in vivo, an osmotic mini-pump was subcutaneously implanted for continuous infusion of AII (400 ng/kg/min). Whole-body HT (43 degrees C, 20 min) was applied 24 h before and 7, 14, and 21 days after the start of the AII infusion. Repeated HT led to the induction of HSP72 expression, which resulted in an attenuation of AII-induced left atrial fibrosis. In an electrophysiological study using isolated perfused heart, continuous AII caused slowing of interatrial conduction without affecting atrial refractoriness. In AII-treated hearts, extrastimuli from the right atrial appendage resulted in a high incidence of repetitive atrial responses, which were suppressed by treatment with HT. Our results suggest that HT treatment is effective in suppressing AII-mediated atrial fibrosis and AF via induction of HSP72 at least in parts, and is thus expected to be a novel strategy for prevention of AF.
authors: Department of Internal Medicine 1, Faculty of Medicine, Oita University, Oita, 1-1 Idaigaoka, Hasama, Oita 879-5593, Japan.
authors: Osamu
authors: O
authors: Wakisaka
authors: Naohiko
authors: N
authors: Takahashi
authors: Tetsuji
authors: T
authors: Shinohara
authors: Tatsuhiko
authors: T
authors: Ooie
authors: Mikiko
authors: M
authors: Nakagawa
authors: Hidetoshi
authors: H
authors: Yonemochi
authors: Masahide
authors: M
authors: Hara
authors: Tatsuo
authors: T
authors: Shimada
authors: Tetsunori
authors: T
authors: Saikawa
authors: Hironobu
authors: H
authors: Yoshimatsu
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000517:prevention & control*; D018929:Cell Culture Techniques; D004719:Endomyocardial Fibrosis / Q000209:etiology / Q000517:prevention & control*; D005347:Fibroblasts / Q000166:cytology / Q000473:pathology / Q000502:physiology; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics*; D006325:Heart Atria / Q000503:physiopathology; D006979:Hyperthermia, Induced; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D050884:HSP72 Heat-Shock Proteins; D007295:Inositol Phosphates; D034741:RNA, Small Interfering; D000804:Angiotensin II