期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 291, 期 3, 页码 H1170-H1176出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00150.2006
关键词
C-reactive protein; human aortic endothelial cells; tissue-type plasminogen activator; plasminogen activator inhibitor
资金
- NCCIH NIH HHS [K24-AT-00596] Funding Source: Medline
- NHLBI NIH HHS [HL-074360] Funding Source: Medline
- NIAID NIH HHS [AI-47294] Funding Source: Medline
Monocyte-endothelial cell adhesion is a key early event in atherogenesis. C-reactive protein (CRP), a cardiovascular risk marker, is known to stimulate ICAM and VCAM in human aortic endothelial cells (HAEC) and induces monocyte-endothelial cell adhesion. In this study, we examined the mechanisms by which native CRP promotes monocyte-endothelial cell adhesion under static conditions and tested the effect of CRP on adhesion under shear flow. Incubation of HAEC with CRP (> 25 mu g/ml) upregulated NF-kappa B activity, and this resulted in a significant increase in ICAM (54% increase, P < 0.001), VCAM (41% increase, P < 0.01), and monocyte-endothelial cell adhesion (44% increase, P < 0.02) compared with those of control. Preincubation with antibodies to CD32 and CD64 but not CD16 effectively inhibited this activation. Blocking NF-kappa B activity with inhibitors or a dominant negative inhibitory kappa B significantly decreased ICAM, VCAM upregulation, and subsequent monocyte-endothelial cell adhesion. Preincubation with antibodies to CD32 and CD64 or transient transfection with small interference RNA to CD32 attenuated CRP-induced NF-kappa B activity, ICAM, VCAM, and monocyte-endothelial cell adhesion under static conditions. Also, the Syk kinase inhibitor piceatannol and MG-132, a proteasome degradation inhibitor, produced similar attenuation in NF-kappa B activity, ICAM, VCAM, and adhesion. Furthermore, CRP-activated endothelial cells supported monocyte rolling, arrest, and transmigration in shear flow (2 dyn/cm(2)), and this was also inhibited by preincubation with antibodies to CD32 and CD64. Thus, in HAEC, CRP upregulates monocyteendothelial adhesion by activation of NF-kappa B through engaging the Fc gamma receptors CD32 and CD64.
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