Gene Therapy for Atrial Fibrillation

Research Project

Project/Area Number	25460408
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Human genetics
Research Institution	University of Occupational and Environmental Health, Japan
Principal Investigator	IGARASHI Tomonori 産業医科大学, 産業生態科学研究所, 講師 (60469393)
Co-Investigator(Kenkyū-buntansha)	OGINOSAWA Yasushi 産業医科大学, 医学部, 助教 (20596720) KOHNO Ritsuko 産業医科大学, 医学部, 講師 (20449945)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	遺伝子治療 / 心房細動 / ギャップ結合
Outline of Final Research Achievements	Ten rats were randomized into 2 groups, control and Connexin (Cx) 43 gene delivered rats. Animals were underwent for electrophysiological study after open-chest surgery. In gene delivered group, we induced Cx43 expressing adeno-associated virus into rat atrial myocyte from epicardium surface. Transversus aortic constriction surgery was performed at the end of the surgery. Two months later, rats were underwent for terminal electrophysiological study. We found that intra-atrial conduction time was significantly shortened in Cx43 delivered rats. The number of AF-induced rats in Cx43 delivered rats was greater than control rats. However, there was no difference in atrial refractory periods and atrial action potential durations among the groups. We also observed that the expression of Cx43 in intercalated disk of atrial cardiomyocytes was significantly increased in gene delivered rats. Gene therapy of Cx43 preserved atrial conduction time and prevented AF for long-term periods.