High NOR-1 (Neuron-Derived Orphan Receptor 1) Expression Strengthens the Vascular Wall Response to Angiotensin II Leading to Aneurysm Formation in Mice

No drug therapy has shown to limit abdominal aortic aneurysm (AAA) growth or rupture, and the understanding of disease biology is incomplete; whereby, one challenge vascular medicine development good animal models therapies for this life-threatening condition. The nuclear receptor NOR-1 (neuron-derived orphan 1) controls biological processes involved in AAA; however, whether it plays a role pathology unknown. Through gain-of-function approach we assessed impact expression on response Ang II (angiotensin II). We used 2 mouse that overexpress human vasculature, them specifically smooth muscle cells. transgenesis amplifies enhancing inflammation (production proinflammatory cytokines, chemokines, reactive oxygen species), increasing MMP (matrix metalloproteinase) activity disturbing elastin integrity, thereby broking resistance C57BL/6 mice II-induced AAA. Genes encoding proteins critically AAA formation ( Il [interleukin]-6 , Il-1? Cxcl2 [C-X-C motif chemokine ligand 2], Mcp-1 [monocyte chemoattractant protein 1] Mmp2 ) were upregulated aneurysmal tissues. Both show similar incidence severity AAA, suggesting high cell sufficient condition strengthen II. These alterations, including formation, prevented by inhibitor doxycycline. Microarray analysis identified gene sets could explain susceptibility transgenic animals aneurysms, those related with extracellular matrix remodeling, inflammatory/immune response, sympathetic activity, differentiation. results involve validate overexpressing as useful experimental models.