Abstract 1563: Angiotensin II Type 2 Receptor Expression and CD34 Progenitor Cell Co-localization in Aortic Aneurysm

Abstract

Altered expression of angiotensin II type-1 and type-2 receptors (AT1, AT2) has been implicated in the development of aortic aneurysm. We used immunohistochemistry to examine the expression of AT1 and AT2 in thoracic and abdominal aortic aneurysm. Thoracic and abdominal aortic tissue samples were collected from organ donor subjects (normal controls; 4M, 9F; age 40±12yr, mean ± SD), and subjects with Marfan syndrome (MFS; 6M, 3F; 42±24yr), bicuspid aortic valve (BAV; 10M, 4F; 62±17yr) or abdominal aortic aneurysm (AAA; 8M, 2F; 72±10). In each type of aneurysm there was mild expression of AT1 and moderate expression of AT2 associated with intimal thickening and the tunica adventitia compared to mild expression of AT1 and negligible expression of AT2 in control aorta. In aneurysm tissue AT1 and AT2 expression, transforming growth factor (TGF)-beta1 expression and progenitor cell (CD34+) localization were also present in areas of tissue remodeling associated with focal medial degeneration, angiogenesis and areas of inflammation. In cell culture experiments aortic fibroblasts (AF) derived from adventitial aneurysm tissue showed moderate expression of AT1 and strong expression of AT2 while control AF showed mild expression of AT1 and negligible expression of AT2. Negligible to mild expression of active TGF-beta1 was observed in all cultured AF. Interestingly adventitial aneurysm cultured in endothelial growth media resulted in the appearance of spindle shaped cells with CD31+ endothelial colonies sprouting among them. Moderate active TGF-beta1 and AT1 and strong AT2 expression were observed in these CD31+ cells. Cultured control adventitia only had spindle cell outgrowth and negligible active TGF-beta1, AT1 and AT2 expression. In summary aneurysm tissue and cultured AF and CD31+ cells of aneurysm origin showed increased expression of AT2 and an absence of increased AT1 expression. Increased AT2 expression in areas of pathological remodeling suggests an active role for AT2 in aneurysm development. Co-localization of increased AT2 with active TGF-beta1 expression and CD34+ cells suggests a role for AT2 in endothelial differentiation and angiogenesis.