Investigating the role of Angiotensin 1-9 in cardiomyocytes hypertrophy

Flores-Muñoz, Monica (2010) Investigating the role of Angiotensin 1-9 in cardiomyocytes hypertrophy. PhD thesis, University of Glasgow.

Abstract

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.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Renin-angiotensin system, hypertrophy, Angiotensin 1-9
• Subjects: R Medicine > R Medicine (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Supervisor's Name: Nicklin, Dr. Stuart A.
• Date of Award: 2010
• Depositing User: Miss Monica Flores-Munoz
• Unique ID: glathesis:2010-1898
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 09 Jun 2010
• Last Modified: 10 Jun 2013 15:11
• URI: https://theses.gla.ac.uk/id/eprint/1898