Investigating the role of Angiotensin 1-9 in cardiomyocytes hypertrophy.
PhD thesis, University of Glasgow.
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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.
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