Tohoku J. Exp. Med., 2011, 225(1)

Semaphorin 3A Attenuates Electrical Remodeling at Infarct Border Zones in Rats after Myocardial Infarction

HUA-ZHI WEN,¹ HONG JIANG,² LI LI,¹ PING XIE,¹ JIN-YAO LI,² ZHI-BING LU² and BO HE²

¹Department of Cardiology, Renmin Hospital of Gansu Province, Lanzhou, P.R. China
²Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China

Electrical remodeling at infarct border zone has been shown to contribute to the occurrence of ventricular arrhythmias after myocardial infarction (MI). Electrical remodeling is causally associated with sympathetic neural remodeling in MI. Semaphorin 3A (Sema3A), a potent neural chemorepellent for sympathetic axons, has been demonstrated to suppress sympathetic neural remodeling after MI. In the present study, we investigated whether treatment with Sema3A can ameliorate electrical remodeling at infarct border zones using a rat model of MI. Wistar rats underwent sham operation (n = 20), the ligation of left coronary artery (MI group, n = 30), MI with control adenovirus (Ad group, n = 30), and MI with Sema3A adenovirus (Sema3A group, n = 30). Eight weeks after treatment, electrophysiological properties including heart rate variability (HRV), monophasic action potential duration (MAPD) and effective refractory period (ERP) and the expression of arrhythmia-related ion channel proteins including Kv4.2, KChIP2 and Kir2.1 at the infarcted border of the left ventricle were examined. These channel proteins may be required for maintaining normal heart rhythm. Compared with the Ad group, Sema3A significantly increased HRV and shortened MAPD and ERP (all p < 0.05). The expression levels of Kv4.2, KChIP2 and Kir2.1 proteins were significantly decreased in MI group and Ad group, compared to sham control. In contrast, the expression levels of these proteins were restored in Sema3A group, which may represent the molecular basis of the Sema3A-mediated inhibition of electrical remodeling. In conclusion, Sema3A can ameliorate electrical remodeling at infarct border zones after MI.

keywords —— arrhythmia; electrical remodeling; myocardial infarction; semaphorin 3A; sympathetic nerve

© 2011 Tohoku University Medical Press

===============================

Tohoku J. Exp. Med., 2011, 225, 51-57

Correspondence: Hong Jiang, Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan 430060, P.R. China.

e-mail: Hong_ j2007@163.com