Novel mechanism for the small G protein-mediated formation and maintenace of vessels

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08627
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Shiga University of Medical Science
• Principal Investigator: OGITA Hisakazu 滋賀医科大学, 医学部, 教授 (50379236)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 血管 / 低分子量Gタンパク質 / 細胞接着

Outline of Final Research Achievements

I investigated the novel function of small G protein RhoA in vascular endothelium and smooth muscle. First, vascular endothelium- and smooth muscle-specific RhoA conditional knockout (cKO) mice were successfully generated by using the Cre-loxP system. I found that vascular endothelium-specific RhoA cKO mice were embryonic lethal due to the insufficiency of the formation of mature vasculature. On the other hand, vascular smooth muscle-specific RhoA cKO mice were born with normal external appearance. When both angiotensin II and BAPN were administered in the mice to induce vascular stress, the occurrence of aortic aneurysm was significantly high, compared with control mice. Based on these results, RhoA plays an important role in the formation and maintenance of blood vessels from the embryonic period to the adulthood.

Free Research Field

生化学、循環器内科

Academic Significance and Societal Importance of the Research Achievements

動脈硬化などによる血管の障害や先天性の血管形成異常は、治療に難渋したり病態が不明なことも多い。本研究の成果は、これらの血管疾患の病態を全面的に解明する端緒となり、また、新規治療開発の基盤として活用できる。特に、超高齢社会の日本で増加している高血圧などの生活習慣病による致死的な血管病（大動脈瘤など）の新たな病態を明らかにすることができ、その対処法の道筋を示すことに貢献できた。