Abstract 10983: Pioglitazone Attenuates Inflammatory Atrial Fibrosis and Vulnerability to Atrial Fibrillation Induced by Pressure Overload in Rats
Background: We tested the hypothesis that atrial fibrosis and increased vulnerability to atrial fibrillation (AF) evoked by pressure overload could be attenuated by pioglitazone, a peroxisome proliferator-activated receptor γ agonist, via suppression of inflammatory profibrotic signals.
Methods and Results: Male Sprague-Dawley rats were underwent abdominal aorta constriction (AAC). Pioglitazone (3 mg/kg/day) or vehicle was orally administered for 4 weeks. We observed followings. 1) Serum C-reactive protein was increased by AAC, which was reversed by pioglitazone. 2) Western blot analysis revealed that AAC enhanced the expression of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-β1 and α-smooth muscle actin in left atrium (LA), which were suppressed by pioglitazone. 3) Messenger RNA expression of collagen type 1 and atrial natriuretic peptide in LA was increased by AAC, which was suppressed by pioglitazone. 4) Gelatin zymography demonstrated that the activity of matrix metalloproteinase-9 was increased by AAC, which was suppressed by pioglitazone. 5) Pioglitazone attenuated AAC-induced LA fibrosis, when assessed by Sirius Red staining. 6) In isolated-perfused heart experiments, AAC did not alter the refractory period of LA and right atrium (RA), but prolonged inter-atrial conduction time (IACT). Programmed extrastimuli from RA induced AF in all of AAC-treated rats (8/8, 100%), which was suppressed by pioglitazone (2/8, 25%, p<0.05) with normalization of IACT.
Conclusions: Our results suggest that inflammatory profibrotic mechanisms are involved in our pressure-overloaded AF model. The results also suggest that pioglitazone is effective to attenuate atrial fibrosis, possibly via suppression of MCP-1-mediated inflammatory profibrotic processes.
- © 2010 by American Heart Association, Inc.