ANGIOTENSIN-II-INDUCED LEUKOCYTE ADHESION ON HUMAN CORONARY ENDOTHELIAL-CELLS IS MEDIATED BY E-SELECTIN

Clinical data suggest a link between the activation of the renin-angio tensin system and cardiovascular ischemic events. Leukocyte accumulati on in the vessel wall is a hallmark of early atherosclerosis and plaqu e 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 endoth elial cells and have been found to be expressed in atherosclerotic pla ques. We investigated whether angiotensin II, the effector of the reni n-angiotensin system, influences the endothelial expression of E-selec tin, VCAM-1, and ICAM-1. In coronary endothelial cells derived from ex planted human hearts, angiotensin II (10(-11) to 10(-5) mol/L) induced a concentration-dependent increase in E-selectin expression. The effe ct was measured by cell ELISA and duplex reverse-transcription polymer ase chain reaction (RT-PCR) and reached its maximum at 10(-7) mol/L. A ngiotensin II induced only a small increase in E-selectin expression i n cardiac microvascular endothelial cells. VCAM-1 and ICAM-1 were not affected by angiotensin II stimulation. In addition, the effect of ang iotensin II-induced E-selectin expression on leukocyte adhesion was qu antified under how conditions. Angiotensin II (10(-7) mol/L) increased leukocyte adhesion significantly to 67% of the maximal effect by tumo r necrosis factor-alpha at a wall shear stress of 2 dyne/cm(2). This a dhesion was found to be E-selectin dependent, as demonstrated by block ing antibodies. The AT(1)-receptor antagonist DUP 753 significantly re duced E-selectin-dependent adhesion, whereas the AT(2)-receptor antago nist PD 123177 had no inhibitory effect. In addition, only AT(1)-recep tor, but not AT(2)-receptor, mRNA could be detected by RT-PCR in coron ary endothelial cells. Therefore, it is suggested that AT, receptors m ediate the effects of angiotensin II on E-selectin expression and leuk ocyte adhesion on coronary endothelial cells.