2019 Fiscal Year Final Research Report
The pathophysiological significance of receptor-binding cardiovascular protective molecule in aging-associated cardiovascular diseases
| Project/Area Number |
17K09313
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
General internal medicine(including psychosomatic medicine)
|
|---|
| Research Institution | Yokohama City University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
山下 暁朗 横浜市立大学, 医学部, 准教授 (20405020)
田村 功一 横浜市立大学, 医学研究科, 教授 (40285143)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Keywords | 心血管病 / 老化 / レニンアンジオテンシン系 / 腎線維化 / サーチュイン |
|---|
| Outline of Final Research Achievements |
The AT1 receptor (AT1R)-associated protein (ATRAP) is a molecule specifically interacting with the carboxyl-terminal domain of AT1R. The results of in-vitro studies showed that ATRAP suppresses Ang II-mediated pathological responses in cardiovascular cells by promoting AT1R internalization. With respect to the tissue distribution and regulation of ATRAP expression in vivo, ATRAP is broadly expressed in many tissues as is AT1R. Accumulating evidence indicates that a tissue-specific regulatory balancing of ATRAP and AT1R expression may be involved in the modulation of AT1R pathological signaling at local tissue sites and also in the pathophysiology of aging-associated cardiovascular diseases.
We herein report that ATRAP plays an important role in inhibiting kidney aging, possibly through sirtuin1-mediated mechanism independent of blocking AT1R signaling, and further protecting normal life span.
|
| Free Research Field |
老年医学
|
| Academic Significance and Societal Importance of the Research Achievements |
ATRAPが，AT1受容体結合性機能選択的制御作用とは異なる，腎臓近位尿細管細胞に及ぼす新規機能として，腎臓線維化抑制作用、抗加齢制御作用を発揮する可能性が高いことを明らかにした．ATRAPは腎老化および個体寿命に対して保護的に作用し，その機序はアンジオテンシン非依存性でSirt1を介している可能性が示唆された.
|
