Abstract 13378: SDPR/Cavin-2 in Endothelial Cells Contributes to Inflammatory Cell Adhesion in Abdominal Aortic Aneurysm

Introduction:Abdominal aortic aneurysm (AAA) is a common and life-threatening vascular disease. Vascular inflammation is the initial phase of aneurysm progression. Adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in the endothelium, play a crucial role to recruit inflammatory cells. Serum deprivation response (SDPR)/Cavin-2 is abundant in endothelial cells. As some of the caveolae-associated proteins are involved in AAA formation, we explored the role of SDPR in vascular inflammation.Hypothesis:SDPR in endothelial cells modulates AAA development through vascular inflammation.Methods:CaCl2-induced AAAs were induced by periaortic application of 0.5 M CaCl2in male SDPR-null and Wild-type (WT) mice at 8-10 weeks of age. Inflammatory response and cell adhesion were evaluated using by human aortic endothelial cells (HAECs) and human monocytes (THP-1 cells).Results:Six weeks after CaCl2treatment, WT mice displayed AAA formation, whereas SDPR-null mice showed the attenuation of AAA development. Elastin degradation in the aortic walls was observed in WT mice after CaCl2treatment, while it was significantly attenuated in SDPR-null mice after CaCl2treatment. The aortic wall infiltration of F40/80-positive macrophages was decreased in SDPR-null mice compared with WT mice. In HAECs, TNF?-induced VCAM-1 protein expression was increased in a time-dependent manner, whereas the expression was suppressed in SDPR-knockdown HAECs. For the evaluation of the adhesion ability, THP-1 cells were co-cultured with TNF?-pretreated HAEC monolayers. The number of THP-1 cells adhered to SDPR-knockdown HAECs was decreased compared with that of control HAECs.Conclusion:SDPR deficiency attenuated AAA formation with the suppression of elastin degradation and macrophage infiltration in CaCl2-induced AAA mice. SDPR-knockdown in endothelial cells suppressed TNF?-induced VCAM-1 expression and inhibited monocyte adhesion. Our results suggest that SDPR in the endothelial cells is associated with VCAM-1-mediated inflammatory cell adhesion.