Abstract 1081: Induction of Heat-Shock Protein 72 Prevents Angiotensin II-Mediated Atrial Fibrosis and Fibrillation in Rat Heart
Atrial fibrillation (AF) is a common arrhythmia and is promoted by an activation of the renin-angiotensin system. We tested the hypothesis that angiotensin II (AII)-mediated atrial fibrosis and AF could be prevented by an induction of heat-shock protein 72 (HSP72). In cultured rat atrial fibroblasts, hyperthermia (HT; 42°C) was applied for 30 min. Twenty-four hours later, AII (100 nmol/L) was added to the medium, and cells were collected. In male rats in vivo, an osmotic mini-pump was subcutaneously implanted for continuous infusion of AII (400 ng·kg−1·min−1). Whole-body HT (43°C, 20 min) was applied 24 hours before and 7, 14 and 21 days after the start of AII infusion. On day 28, each heart was isolated. In the cultured atrial fibroblasts, we observed that HT induced HSP72 expression, which was associated with the attenuation of AII-induced extracellular signal-regulated kinase (ERK1/ERK2) phosphorylation and α-smooth muscle actin (α-SMA) expression. The small interfering RNA (siRNA) targeting HSP72 abolished these anti-fibrotic effects of HT in the fibroblasts. In rats in vivo, HT resulted in an attenuation of AII-induced left atrial fibrosis. In an electrophysiological study using isolated-perfused heart, continuous AII infusion caused interatrial conduction slowing without affecting atrial refractoriness. In AII-treated hearts, extrastimuli from the right atrial appendage resulted in a high incidence of repetitive atrial responses (RARs, 7/8, 88%), which were suppressed by pretreatment with HT (3/8, 38%, p<0.05). Our results suggest that induction of HSP72 is effective in suppressing AII-mediated atrial fibrosis and AF, and is thus expected to be a novel strategy for AF prevention.