Low shear stress regulates monocyte adhesion to oxidized lipid-induced endothelial cells via an IkappaBalpha dependent pathway.
In regions of a vessel that experience low shear stress and reversing flow patterns, early features in the pathogenesis of atherosclerosis include the accumulation of oxidized LDL (OxLDL) and adhesion of monocytes to endothelial cells (EC). Here we investigated the hypothesis that low shear stress (2 dyn/cm2) and OxLDL are synergistic for enhanced expression of vascular cell adhesion molecule (VCAM-1) and human aortic endothelial cell (HAEC)-monocyte adhesion. This study shows low shear stress can significantly reduce IkappaBalpha levels, activate NF-kappaB, increase the expression of VCAM-1 in HAEC and binding of monocytes. OxLDL itself cannot significantly increase the expression of VCAM-1 in HAEC and binding of monocytes, but through activation of NF-kappaB and degradation of IkappaBalpha induced by low shear stress it can significantly enhance VCAM-1 expression and monocyte adhesion, over that in unmodified LDL or control. These results suggest that low shear stress can regulate monocyte adhesion to oxidized lipid-induced endothelial cells via an IkappaBalpha-dependent pathway, and that low shear stress together with OxLDL may likely play an important role in atherogenesis.
Zhu
Chu-hong
CH
Department of Anatomy, Biomechanics Section under the Key Lab for Biomechanics & Tissue Engineering of Ministry of Education, Third Military Medical University, Chongqing, China.
Ying
Da-jun
DJ
Mi
Jian-hong
JH
Zhu
Xing-hong
XH
Sun
Jian-sen
JS
Cui
Xiao-ping
XP
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000502:physiology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D020672:I-kappa B Proteins; D008077:Lipoproteins, LDL; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; D000072000:NF-KappaB Inhibitor alpha