Role of Caveolae in the development of abdominal aortic aneurysms

Abdominal aortic aneurysm (AAA) is a major cardiovascular disease and involves enhancement of rennin‐angiotensin system and recruitment/activation of inflammatory factors such as matrix metalloproteinases (MMP's). Caveolae has been shown to play a role in a number of different cardiovascular diseases through different mechanisms including regulation of oxidative stress, inflammation and degradation of extracellular matrix components through MMP's. In addition, endothelial cell caveolae are known to localize the Ang‐II (AT1) receptor and regulate rennin‐angiotensin signaling. Based on these findings, we evaluated the role of caveolae in a murine model of AAA formation. Here, eight week old mice were co‐infused with AngII and BAPN, a lysyl oxidase inhibitor, to induce AAA. We found that mice lacking the main structural protein of caveolae, caveolin‐1, did not develop AAA compared to WT animals in spite of hypertensive blood pressures measured by telemetry in both groups. This finding suggests that intact Ang‐II signaling remains in place in caveolin‐1 knockout mice. To begin to address the underlying mechanism by which caveolae contributes to AAA, we measured the level of oxidative stress and MMP's in aneurysms. We found an increased expression of MMP‐2 and MMP‐9 in vessels of WT mice displaying aneurysms. This increase in expression was not observed in Cav‐1 knockout mice. Furthermore, KO mice showed less oxidative stress then their WT counterparts as assessed by anti‐nitrotyrosine staining. In conclusion, caveolae appears to play a critical role in the formation of AAA in mice via oxidative stress, and recruitment and/or activation of MMPs, specifically MMP‐2 and MMP‐9.