Flow-dependent increase of ICAM-1 on saphenous vein endothelium is sensitive to apamin

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 287; no. 1; pp. H22 - H28
• Main Authors: Sultan, Sabena, Gosling, Martin, Abu-Hayyeh, Shadi, Carey, Nessa, Powell, Janet T
• Format: Journal Article
• Language: English
• Published: United States 01.07.2004
• Subjects: Apamin - pharmacology; Calcium - metabolism; Cells, Cultured; Chelating Agents - pharmacology; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Humans; Intercellular Adhesion Molecule-1 - metabolism; Intracellular Membranes - metabolism; Potassium Channel Blockers - pharmacology; Potassium Channels, Calcium-Activated - metabolism; Regional Blood Flow - physiology; Saphenous Vein - cytology; Saphenous Vein - physiology; Stress, Mechanical
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00880.2003

Department of Vascular Surgery, Imperial College at Charing Cross, London W6 8RP, United Kingdom Submitted 7 October 2003 ; accepted in final form 9 February 2004 The potassium channel blocker tetraethylammonium blocks the flow-induced increase in endothelial ICAM-1. We have investigated the subtype of potassium channel that modulates flow-induced increased expression of ICAM-1 on saphenous vein endothelium. Cultured human saphenous vein endothelial cells (HSVECs) or intact saphenous veins were perfused at fixed low and high flows in a laminar shear chamber or flow rig, respectively, in the presence or absence of potassium channel blockers. Expression of K + channels and endothelial ICAM-1 was measured by real-time polymerase chain reaction and/or immunoassays. In HSVECs, the application of 0.8 N/m 2 (8 dyn/cm 2 ) shear stress resulted in a two- to fourfold increase in cellular ICAM-1 within 6 h ( P < 0.001). In intact vein a similar shear stress, with pulsatile arterial pressure, resulted in a twofold increase in endothelial ICAM-1/CD31 staining area within 1.5 h ( P < 0.001). Both increases in ICAM-1 were blocked by inclusion of 100 nM apamin in the vein perfusate, whereas other K + channel blockers were less effective. Two subtypes of small conductance Ca 2+ -activated K + channel (selectively blocked by apamin) were expressed in HSVECs and vein endothelium (SK3>SK2). Apamin blocked the upregulation of ICAM-1 on saphenous vein endothelium in response to increased flow to implicate small conductance Ca 2+ -activated K + channels in shear stress/flow-mediated signaling pathways. cardiovascular surgery; endothelial function; hemodynamics; K + channel Address for reprint requests and other correspondence: S. Sultan, Centre for Cardiovascular Biology and Medicine, BHF Laboratories, Dept. of Medicine, Univ. College London, 5 University St., London, WC1E 6JJ, UK (E-mail: s.sultan{at}ucl.ac.uk ).