Arterial and Venous Endothelia Display Differential Functional Fractalkine (CX(3)CL1) Expression by Angiotensin-II

作者：Rius Cristina; Piqueras Laura; Gonzalez Navarro Herminia; Albertos Fernando; Company Chantal; Lopez Gines Concha; Ludwig Andreas; Blanes Jose Ignacio; Morcillo Esteban J; Sanz Maria Jesus^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2013, 33(1): 96-+.

DOI：10.1161/ATVBAHA.112.254870

• angiotensin-II
• arterial endothelium
• CX3CL1
• endothelial dysfunction
• mononuclear cells

Objective-Angiotensin-II (Ang-II) promotes the interaction of mononuclear cells with arterioles and neutrophils with postcapillary venules. To investigate the mechanisms underlying this dissimilar response, the involvement of fractalkine (CX(3)CL1) was explored. %26lt;br%26gt;Methods and Results-Enhanced CX(3)CL1 expression was detected in both cremasteric arterioles and postcapillary venules 24 hours after Ang-II intrascrotal injection. Arteriolar leukocyte adhesion was the unique parameter significantly reduced (83%) in animals lacking CX(3)CL1 receptor (CX(3)CR1). Human umbilical arterial and venous endothelial cell stimulation with 1 mu mol/L Ang-II increased CX(3)CL1 expression, yet neutralization of CX(3)CL1 activity only significantly inhibited Ang-II-induced mononuclear cell-human umbilical arterial endothelial cell interactions (73%) but not with human umbilical venous endothelial cells. The use of small interfering RNA revealed the involvement of tumor necrosis factor-alpha in Ang-II-induced CX(3)CL1 upregulation and mononuclear cell arrest. Nox5 knockdown with small interfering RNA or pharmacological inhibition of extracellular signal-regulated kinases1/2, p38 mitogen-activated protein kinase, and nuclear factor-kappa B also abolished these responses. Finally, when human umbilical arterial endothelial cells were costimulated with Ang-II, tumor necrosis factor-alpha, and interferon-gamma, CX(3)CL1 expression and mononuclear cell adhesiveness were more pronounced than when each stimulus was provided alone. %26lt;br%26gt;Conclusion-These results suggest that Ang-II induces functional CX(3)CL1 expression in arterial but not in venous endothelia. Thus, targeting endothelial CX(3)CL1-mononuclear leukocyte CX(3)CR1 interactions may constitute a new therapeutic strategy in the treatment of Ang-II-associated cardiovascular diseases. (Arterioscler Thromb Vasc Biol. 2013;33:96-104.)

• 出版日期2013-1