Abdominal aortic aneurysms are characterized by degradation of aortic wall elastin and collagen fibers resulting in diminished tensile strength and aneurysmal dilatation. It is also an extreme form of vascular remodeling, with both a fibroproliferative and chronic inflammatory state. Angiotensin 2 (Ang II) promotes both of these findings in atherosclerotic lesions, and the use of certain angiotensin converting enzyme inhibitors can alter such vascular remodeling. It has been implicated that the angiotensin type 1 receptor mediates most of the cellular effects seen by Ang II, however, new evidence suggests that angiotensin type 2 receptors also plays a crucial role in apopotosis and may exert effects on mesenchymal and infiltrating cell types. We propose to examine the role of AT2 receptors in the development of aneurysms using the elastase induced mouse model. We will examine in our model the expression of Ang II forming enzymes, ACE and chymase, using immunohistochemistry, immunoblotting, and RT-PCR. Also, the expression of AT1 and AT2 receptors will be characterized in the aortic wall and in infiltrating cells. Lastly, using gene-disrupted mice of either AT1 and AT2, we will see if aneurysm formation is attenuated in our mouse model.
