Abstract 11941: Importance of VEGF Mediated Pulmonary Vein Fibrosis on Atrial Fibrillation Promotion in Hypertensive Rat Heart
Background: Hypertension is one of the independent risk factors for atrial fibrillation (AF). Recently, pulmonary veins (PVs) play an important role in the substrate of AF as well as trigger of AF, although underlying mechanisms are poorly understood. The purpose of this study was to determine the importance of PVs fibrosis on AF promotion in hypertensive rat heart.
Methods and Results: Eighteen-week Dahl salt-sensitive hypertensive (HT) rats and their controls were used for histological analysis and electrophysiological study (EPS) in Langendorff perfused heart with PVs and lungs. Masson-trichrome staining revealed that HT induced fibrosis area was significantly increased in PV as compared with left atrium (LA) in both HT and control rats. Especially, PV fibrosis was prominent in HT rats rather than controls (Figure A). EPS in HT rat with PVs significantly increased the number of repetitive atrial responses (RAR) which could be significantly diminished after excision of PVs (i.e. PV isolation) (Figure B). There were no differences in the ERP of atrium between HT and control rats (HT: 33±2 msec vs. control: 35±1 msec, p=NS). Immunofluorecense analyzing from HT rat tissue samples revealed that smooth muscle cells neighboring the endothelial cells in PVs showed remarkable proliferation with VEGF expression whereas there were no smooth muscle cells in the subendocardium of LA. Pretreatment with imatinib (20mg/kg/day) in HT rats reduced smooth muscle cell proliferation in PVs along with the reduction of VEGF expression. PV fibrosis was dramatically reduced by pretreatment with imatinib in HT rats. Imatinib treated HT rats also effectively prevented RAR promotion during EPS before PV isolation without affecting high systolic blood pressure (Figure A & B).
Conclusion: VEGF mediated PV specific fibrosis might play an important component in arrhythmogenic substrate of AF in hypertensive rat heart.
- © 2013 by American Heart Association, Inc.