Endothelial cell-specific deficiency of @entity15395 type 1a receptors attenuates @entity15395 -induced ascending XXXX in @entity1748 -/- @entity19 .

@entity1 @entity1748 @entity449 @entity19 @entity15395 @entity21823 @entity439 @entity1886 @entity1129
RATIONALE: @entity1 studies and @entity19 models have provided evidence for @entity15395 ( @entity15395 )-based mechanisms as an underlying cause of @entity439 localized to the ascending aorta. In agreement with this associative evidence, we have published recently that @entity15395 infusion induces aneurysmal pathology in the ascending aorta. OBJECTIVE: The aim of this study was to define the role of @entity15395 type 1a ( @entity1129 (1a)) receptors and their cellular location in @entity15395 -induced ascending @entity449 ( @entity449 ). METHODS AND RESULTS: Male @entity1748 (-/-) @entity19 were fed a saturated fat-enriched diet for 1 week before osmotic mini-pump implantation and infused with either saline or @entity15395 (1000 ng/kg per minute) for 28 days. Intimal surface areas of ascending aortas were measured to quantify ascending @entity449 . Whole body @entity1129 (1a) receptor deficiency ablated @entity15395 -induced ascending @entity449 (P<0.001). To determine the role of @entity1129 (1a) receptors on leukocytes, @entity1748 (-/-) @entity1129 (1a) receptor(+/+) or @entity1129 (1a) receptor(-/-) @entity19 were irradiated and repopulated with bone marrow-derived cells isolated from either @entity1129 (1a) receptor(+/+) or @entity1129 (1a) receptor(-/-) @entity19 . @entity1129 (1a) receptors in bone marrow-derived cells had no effect on @entity15395 -induced ascending @entity449 . To determine the role of @entity1129 (1a) receptors on vascular wall cells, we developed @entity1129 (1a) receptor floxed @entity19 with depletion on either smooth muscle or endothelial cells using Cre driven by either @entity21823 or @entity1886 , respectively. @entity1129 (1a) receptor deletion in smooth muscle cells had no effect on ascending @entity449 . In contrast, endothelial-specific depletion attenuated this pathology. CONCLUSIONS: @entity15395 infusion promotes @entity439 in the ascending aorta via stimulation of @entity1129 (1a) receptors that are expressed on endothelial cells.
