The pathophysiological significance of receptor-binding molecule in cardiovascular diseases based on insulin resistance

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21318
• Project/Area Number (Other): 18H06215 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Yokohama City University
• Principal Investigator: Kohji Ohki 横浜市立大学, 医学研究科, 客員研究員 (60828713)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 高血圧 / アンジオテンシン受容体 / 尿細管 / インスリン抵抗性

Outline of Final Research Achievements

The AT1 receptor (AT1R)-associated protein (ATRAP) is a molecule specifically interacting with the carboxyl-terminal domain of AT1R so as to inhibit hyperactivation of its downstream signaling.Although ATRAP expression is abundant in renal proximal tubules, little is known about the actual function of renal proximal tubule ATRAP in angiotensin II-mediated hypertension. We generated proximal tubule specific ATRAP knockout (PT-KO) mice using the Cre/loxP system with Pepck-Cre. ATRAP mRNA expression decreased by 80% in proximal regions of the nephron in PT-KO mice compared with wild-type (WT) mice. Blood pressure of PT-KO mice was comparable with that of WT mice at baseline. Moreover, no significant differences were noted in pressor response and cardiac hypertrophy to angiotensin II infusion between PT-KO and WT mice. The results indicate that renal proximal tubule ATRAP has a minor role in angiotensin II-mediated hypertension.

Free Research Field

腎臓学、高血圧学

Academic Significance and Societal Importance of the Research Achievements

今回の実験結果と我々の過去の報告を総合すると、アンジオテンシン依存性高血圧の病態形成に腎近位尿細管ATRAPが果たす役割は小さく、腎ATRAPは主に腎遠位尿細管ATRAPを介したメカニズムによりアンジオテンシン依存性高血圧を抑制すると考えられた。