Cell Type–Specific Contributions of the Angiotensin II Type 1a Receptor to Aorta Homeostasis and Aneurysmal Disease—Brief Report

Objective—Two were the aims of this study: first, to translate whole-genome expression profiles into computational predictions of functional associations between signaling pathways that regulate aorta homeostasis and the activity of angiotensin II type 1a receptor (At1ar) in either vascular endothelial or smooth muscle cells; and second, to characterize the impact of endothelial cell– or smooth muscle cell–specific At1ar disruption on the development of thoracic aortic aneurysm in fibrillin-1 hypomorphic (Fbn1mgR/mgR) mice, a validated animal model of early onset progressively severe Marfan syndrome. Approach and Results—Cdh5-Cre and Sm22-Cre transgenic mice were used to inactivate the At1ar-coding gene (Agt1ar) in either intimal or medial cells of both wild type and Marfan syndrome mice, respectively. Computational analyses of differentially expressed genes predicted dysregulated signaling pathways of cell survival and matrix remodeling in Agt1arCdh5−/− aortas and of cell adhesion and contractility in Ag...