Oxidized lipoprotein(a) enhanced the expression of P-selectin in cultured human umbilical vein endothelial cells.
Lipoprotein(a) [Lp(a)] has been demonstrated to be an independent risk factor for coronary heart disease. However, the precise mechanism by which it contributes to the development of atherosclerosis remains unclear. P-selectin is one of the major adhesion molecules to mediate the interaction between monocytes, platelets and endothelial cells. Increased expression of P-selectin has been frequently found in atherosclerotic lesions. The present study assessed the effects of native and oxidized LDL (n-LDL and ox-LDL) and Lp(a) (n-Lp(a) and ox-Lp(a)) on the expression of P-selectin in cultured human umbilical vein endothelial cells (HUVECs). Cell ELISA was used to measure the expression of P-selectin in HUVECs and monocyte adhesion assay was used to detect whether the P-selectin expressed in HUVECs was functional. P-selectin mRNA expression in HUVECs was determined by Northern blot. Results showed that P-selectin protein expression was not influenced by n-LDL, but was moderately increased by ox-LDL and n-Lp(a). ox-Lp(a) was the most potent stimulus for P-selectin expression, increasing it in HUVECs by 144 +/- 10% at 10 nmol/l and 202 +/- 22% at 20 nmol/l. In addition, it showed that dose dependency induced monocyte adherence to endothelial cells after incubation of HUVECs with ox-Lp(a). Northern blot analysis demonstrated that the amount of P-selectin mRNA was markedly increased after treatment with ox-Lp(a) but not with n-LDL, ox-LDL and n-Lp(a). These results demonstrate that ox-Lp(a) can induce P-selectin expression in HUVECs, which may thereby influence the pathogenesis of athersclerosis.
Zhao
S P
SP
Department of Cardiology, the Second Affiliated Hospital, Hunan Medical University, 410011, Changsha, China. zhaosp@public.cs.hn.cn
Xu
D Y
DY
D002448:Cell Adhesion / Q000187:drug effects; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D017270:Lipoprotein(a) / Q000378:metabolism / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology; D019007:P-Selectin / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects
D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D019007:P-Selectin; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein