Abstract 512: Angiotensin II Type 1 Receptor is Essential for the Initiation and Progression of Porcine Pancreatic Elastase-Induced Experimental Abdominal Aortic Aneurysms
Angiotensin (Ang) II type 1 receptor (AT1) activity is critical for experimental abdominal aortic aneurysm (AAA) formation in response to Ang infusion in hyperlipidemic mice. The role of AT1 activity in exogenous Ang II-independent, experimental AAA is unknown. Genetic and pharmacological inhibition strategies were used to isolate the significance of AT1 function in porcine pancreatic elastase (PPE)-induced AAAs in normolipidemic C57BL/6 mice. AAA progression was monitored via serial in-vivo transabdominal ultrasound measurements at 40 mHz. Aortic diameters enlarged remarkably from day 3 to day 14 in control mice following PPE infusion. Progression was abrogated, however, following either targeted AT1a receptor deletion, or treatment with the AT1 inhibitor telmisartan, beginning day 3 prior to PPE infusion. Additionally, telmisartan treatment initiated 4 days following PPE-infusion led to stabilization /regression of existing AAAs. Histologically, AT1a deficiency or telmisartan treatment resulted in preserved medial smooth muscle cellularity and elastic fibers, and attenuated mural angiogenesis and leukocyte infiltration. Telmisartan treatment did not affect PPARγ-regulated gene expression in aneurysmal aortae, however, and the PPARγ antagonist (GW9662) did not influence telmisartan-induced AAA suppression. In conclusion, AT1 activity is required for the initiation and progression of experimental AAAs, independent of the specific methodology used to induce aneurysm formation. Strategies targeting AT1 activity may prove effective in limiting human AAA progression.
- © 2013 by American Heart Association, Inc.