Overexpression of constitutively active NPR-B inhibits cardiac hypertrophy

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461620
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Osaka University
• Principal Investigator: OKADA YOKO 大阪大学, 医学(系)研究科(研究院), 招へい教員 (30457022)
• Co-Investigator(Kenkyū-buntansha): KOGAKI Shigetoyo 大阪大学, 医学(系)研究科(研究院), 講師 (00311754)
• Co-Investigator(Renkei-kenkyūsha): TAKAHASHI Kunihiko 大阪大学, 医学(系)研究科(研究院), 招へい教員 (10610230)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: NPR-B / CNP / cyclic GMP / 心不全

Outline of Final Research Achievements

We have identified a novel missense mutation in the NPR-B gene (2647G>A; Val 883 Met) in a family case showing overgrowth and bone anomalies. Overexpression of this constitutively active NPR-B (MT) induced significant increase in intracellular cGMP levels without CNP binding. We investigated a hypothesis that overexpression of MT inhibits cardiac hypertrophy.
To overexpress MT especially in heart, we used recombinant adeno-associated viral serotype-9 (rAAV-9) vectors. 10-week-old mice were subcutaneously implanted a miniosmotic pump that released isoproterenol. Tail vain injection of rAAV-9 vector was administered after the pump implantation. We investigate the heart body weight ratios (HW/BW), echocardiography, and histological analysis of heart (cell size .etc).As a result, overexpression of MT in heart inhibited ISO-induced cardiac hypertrophy compared to GFP control.
MT-NPRB may be an additional therapeutic target in the treatment of cardiac hypertrophy.

Free Research Field

小児循環器