title: Angiotensin II-induced leukocyte adhesion on human coronary endothelial cells is mediated by E-selectin.
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 athero-sclerotic 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-alpha at a wall shear stress of 2 dyne/cm2. This adhesion was found to be E-selectin dependent, as demonstrated by blocking antibodies. The AT1-receptor antagonist DUP 753 significantly reduced E-selectin-dependent adhesion, whereas the AT2-receptor antagonist PD 123177 had no inhibitory effect. In addition, only AT1-receptor, but not AT2-receptor, mRNA could be detected by RT-PCR in coronary endothelial cells. Therefore, it is suggested that AT1 receptors mediate the effects of angiotensin II on E-selectin expression and leukocyte adhesion on coronary endothelial cells.
authors.affiliation: Department of Internal Medicine/Cardiology, Virchow Klinikum, Humboldt University, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gräfe
authors.forename: W
authors.initials: W
authors.lastname: Auch-Schwelk
authors.forename: A
authors.initials: A
authors.lastname: Zakrzewicz
authors.forename: V
authors.initials: V
authors.lastname: Regitz-Zagrosek
authors.forename: P
authors.initials: P
authors.lastname: Bartsch
authors.forename: K
authors.initials: K
authors.lastname: Graf
authors.forename: M
authors.initials: M
authors.lastname: Loebe
authors.forename: P
authors.initials: P
authors.lastname: Gaehtgens
authors.forename: E
authors.initials: E
authors.lastname: Fleck
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology* / Q000502:physiology; D019040:E-Selectin / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007962:Leukocytes / Q000166:cytology* / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
chemical_list: D019040:E-Selectin; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D018799:Intercellular Adhesion Molecule-1