Investigating the role of Angiotensin 1-9 in cardiomyocytes hypertrophy

R Medicine (General)

Flores-Muñoz, Monica ; Nicklin, Stuart A.

University:University of Glasgow

Department:Institute of Cardiovascular and Medical Sciences

关键词: Renin-angiotensin system, hypertrophy, Angiotensin 1-9;   

Others  :  http://theses.gla.ac.uk/1898/1/2010floresphd.pdf

来源: University of Glasgow

【 摘 要 】

The renin-angiotensin system (RAS) regulates blood pressure, and homeostasis through angiotensin II (AngII). Angiotensin converting enzyme 2 (ACE2), a homologue of ACE, metabolizes AngII to Ang1-7. Ang1-7 antagonizes AngII via the receptor MAS. ACE2 also converts AngI to Ang1-9. Very little is known about Ang1-9 although it is thought to be a substrate for Ang1-7 generation via ACE. We investigated Ang1-9 and Ang1-7 function in cardiomyocyte hypertrophy in rat neonatal and primary adult rabbit left ventricular cardiomyocytes. We have shown that Ang1-7 and Ang1-9 blocked AngII-induced hypertrophy. Furthermore, we demonstrated an independent role of Ang1-9 in cardiac hypertrophy and generated evidence that Ang1-9 signals via the angiotensin type 2 receptor. In vivo we delivered Ang1-9 via osmotic minipumps for 4 weeks into stroke-prone spontaneously hypertensive rats. Delivery of Ang1-9 reduced cardiac fibrosis and improved endothelial function compared to control animals. These findings have implications for our understanding of RAS function.