Flow-dependent increase of ICAM-1 on saphenous vein endothelium is sensitive to apamin
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...
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Published in | American journal of physiology. Heart and circulatory physiology Vol. 287; no. 1; pp. H22 - H28 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.07.2004
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Subjects | |
Online Access | Get full text |
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Summary: | 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 ). |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0363-6135 1522-1539 |
DOI: | 10.1152/ajpheart.00880.2003 |