Angiotensin II–Induced Leukocyte Adhesion on Human Coronary Endothelial Cells Is Mediated by E-Selectin

Abstract

Abstract Clinical data suggest a link between the activation of the renin-angiotensin system and cardiovascular ischemic events. Leukocyte accumulation in the vessel wall is a hallmark of early atherosclerosis and plaque progression. E-Selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) are adhesion molecules participating in mediating interactions between leukocytes and endothelial cells and have been found to be expressed in atherosclerotic plaques. We investigated whether angiotensin II, the effector of the renin-angiotensin system, influences the endothelial expression of E-selectin, VCAM-1, and ICAM-1. In coronary endothelial cells derived from explanted human hearts, angiotensin II (10 −11 to 10 −5 mol/L) induced a concentration-dependent increase in E-selectin expression. The effect was measured by cell ELISA and duplex reverse-transcription polymerase chain reaction (RT-PCR) and reached its maximum at 10 −7 mol/L. Angiotensin II induced only a small increase in E-selectin expression in cardiac microvascular endothelial cells. VCAM-1 and ICAM-1 were not affected by angiotensin II stimulation. In addition, the effect of angiotensin II–induced E-selectin expression on leukocyte adhesion was quantified under flow conditions. Angiotensin II (10 −7 mol/L) increased leukocyte adhesion significantly to 67% of the maximal effect by tumor necrosis factor-α at a wall shear stress of 2 dyne/cm 2 . This adhesion was found to be E-selectin dependent, as demonstrated by blocking antibodies. The AT 1 -receptor antagonist DUP 753 significantly reduced E-selectin–dependent adhesion, whereas the AT 2 -receptor antagonist PD 123177 had no inhibitory effect. In addition, only AT 1 -receptor, but not AT 2 -receptor, mRNA could be detected by RT-PCR in coronary endothelial cells. Therefore, it is suggested that AT 1 receptors mediate the effects of angiotensin II on E-selectin expression and leukocyte adhesion on coronary endothelial cells.