Submitted on April 19, 2006
Accepted on December 19, 2006
Vascular bed origin dictates flow pattern regulation of endothelial adhesion molecule expression
Heiko Methe1*, Mercedes Balcells2, Maria del Carmen Alegret2, Marina Santacana2, Blanca Molins2, Anne Hamik3, Mukesh Jain3, and Elazer Reuven Edelman4
1 HST, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
2 HST, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States; Institut Quimic de Sarria, Universitat Ramon LLull, Barcelona, Spain
3 Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
4 HST, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States; Cardiovascular Division , Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: hmethe{at}mit.edu.
Endothelial cell phenotypes markedly differ depending upon function and vascular bed of origin. Differences might account for specific susceptibility to pathologic 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)-
-stimulated HSVEC were exposed to coronary artery flow in place of physiologic venous flow and 1.9 fold higher compared with attachment to cytokine-stimulated HCAEC exposed to coronary artery flow. This 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--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--induced E-selectin and VCAM-1 expression on HCAEC whereas coronary artery flow further induced ICAM-1 on cytokine-stimulated HCAEC. With 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 EC-types studied. Interestingly, Kruppel-like factors (KLF)4 overexpression in HCAEC and HSVEC significantly augmented TNF--induced E-selectin and VCAM-1 expression in static conditions while ICAM-1 expression remained constant. Furthermore, both flow patterns induced KLF2 and 4 expressionin 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 pathologic conditions.
