title: Vascular bed origin dictates flow pattern regulation of endothelial adhesion molecule expression.
abstract: Endothelial cell phenotypes markedly differ, depending upon function and vascular bed of origin. Differences might account for specific susceptibility to pathological conditions. As leukocyte adhesion to activated endothelium is the initiating event in a range of diseases, we compared the influence of vascular bed-specific flow patterns on adhesion molecule expression in human saphenous vein (HSVEC) and coronary artery endothelial cells (HCAEC). In vitro, immune cell attachment was increased 1.6-fold when tumor necrosis factor (TNF)-alpha-stimulated HSVEC were exposed to coronary artery flow in place of physiological venous flow and 1.9-fold higher compared with attachment to cytokine-stimulated HCAEC exposed to coronary artery flow. This was associated with increased concentrations of soluble E-selectin, VCAM-1, and ICAM-1 in supernatants of HSVEC exposed to coronary artery flow compared with HCAEC exposed to the same flow pattern. Venous and coronary artery flow both increased TNF-alpha-induced E-selectin and ICAM-1 expression on HSVEC, but only coronary artery flow increased VCAM-1 expression. In marked contrast to HSVEC, venous and coronary artery flow attenuated TNF-alpha-induced E-selectin and VCAM-1 expression on HCAEC, whereas coronary artery flow further induced ICAM-1 on cytokine-stimulated HCAEC. With the exception of cytokine-induced ICAM-1, adhesion molecule expression on HSVEC exposed to coronary artery flow exceeded expression on HCAEC. Thus ICAM-1 expression involves complex flow-dependent and -independent pathways with marked dissimilarities between the two endothelial cell types studied. Interestingly, Kruppel-like factor (KLF) 4 overexpression in HCAEC and HSVEC significantly reduced TNF-alpha-induced E-selectin and VCAM-1 expression in static conditions, while ICAM-1 expression remained constant. Furthermore, both flow patterns induced KLF2 and KLF4 expression in HCAEC and HSVEC. Venous and coronary artery flow differentially influence endothelial adhesion molecule and transcription factor expression, depending on the vascular bed of origin. Differences in adhesion molecule expression and subsequent immune cell adhesion between HSVEC and HCAEC may contribute to different susceptibility to pathological conditions.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. hmethe@mit.edu
authors.forename: Heiko
authors.initials: H
authors.lastname: Methe
authors.forename: Mercedes
authors.initials: M
authors.lastname: Balcells
authors.forename: Maria del Carmen
authors.initials: Mdel C
authors.lastname: Alegret
authors.forename: Marina
authors.initials: M
authors.lastname: Santacana
authors.forename: Blanca
authors.initials: B
authors.lastname: Molins
authors.forename: Anne
authors.initials: A
authors.lastname: Hamik
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Jain
authors.forename: Elazer R
authors.initials: ER
authors.lastname: Edelman
mesh_terms: D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D033081:Shear Strength; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015815:Cell Adhesion Molecules; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D014409:Tumor Necrosis Factor-alpha