Contribution of brain renin isoforms to the pathogenesis of heart failure

Research Project

Project/Area Number	17K16012
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Cardiovascular medicine
Research Institution	Kyushu University
Principal Investigator	Shinohara Keisuke 九州大学, 大学病院, 医員 (30784491)
Project Period (FY)	2017-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	心不全 / 脳 / レニン・アンジオテンシン系
Outline of Final Research Achievements	Sympathoexcitation is crucially involved in the pathogenesis of heart failure (HF). Brain renin-angiotensin system (RAS) plays an important role in the regulation of sympathetic activity. Renin is the rate-limiting component of the RAS and there are two renin isoforms: classical secreted renin and novel intracellular renin which remains intracellularly. Intracellular renin has been shown to be predominantly expressed in the brain. We previously generated a unique mouse model by selectively ablating the intracellular renin and indicated that increased secreted renin and decreased intracellular renin in the brain may contribute to sympathetic activation. The aim of this study was to examine whether the secreted renin is increased while the intracellular renin is decreased in post-myocardial infarction-induced HF rat model. We demonstrated that the secreted renin is increased without significant changes in intracellular renin in the brain nuclei regulating sympathetic activity in HF rats.
Academic Significance and Societal Importance of the Research Achievements	心不全は患者数が増加の一途をたどる中、5年生存率50%という未だ予後不良の疾患である。これまでの多くの心不全治療や心不全研究は心臓をはじめとする末梢臓器をターゲットとしてきたが、心不全の病態に重要な交感神経活性化に最も寄与する臓器は脳といえる。本研究で心不全における脳内レニンの発現調節異常を明らかにすることは、心不全に伴う交感神経活性化の機序解明につながり、心不全の新規治療法開発に応用できると考える。