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Wakisaka O, Takahashi N, Shinohara T, Ooie T, Nakagawa M, Yonemochi H, Hara M, Shimada T, Saikawa T, Yoshimatsu H: Hyperthermia treatment prevents angiotensin II-mediated atrial fibrosis and fibrillation via induction of heat-shock protein 72. Zhonghua Jie He He Hu Xi Za Zhi. 2009 Apr;32(4):287-91.
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. |
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