Apolipoprotein(a) is a human vascular endothelial cell agonist: studies on the induction in endothelial cells of monocyte chemotactic factor activity.
Elevated levels of lipoprotein(a), Lp(a), are associated with premature atherosclerosis; however, the mechanisms of its atherogenicity are not known. Recruitment of monocytes to the blood vessel wall is an early event in atherogenesis. Since Lp(a) is associated with macrophages in the plaque, we have examined the effect of Lp(a) on inducing monocyte chemotactic activity (MCA) in vascular endothelial cells. We report that Lp(a) and apo(a) induced human umbilical vein (HUVEC) and coronary artery endothelial cells to secrete monocyte chemotactic activity as early as 30 min of incubation. In the absence of cells, Lp(a) had no direct monocyte chemotactic activity. Actinomycin D and cycloheximide inhibited the HUVEC response, indicating that protein and RNA synthesis were required. Endotoxin was shown not to be responsible for the induction of monocyte chemotactic activity. Granulocyte monocyte-colony stimulating factor antigen was not detected in the Lp(a)-conditioned medium, nor was monocyte chemoattractant protein-1 mRNA induced by Lp(a). These results suggest that Lp(a) may be involved in the recruitment of monocytes to the vessel wall, thus providing a novel mechanism for the participation of Lp(a) in the atherogenic process.
Poon
M
M
Division of Cardiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Zhang
X
X
Dunsky
K
K
Taubman
M B
MB
Harpel
P C
PC
D001054:Apolipoproteins A / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054410:Chemokine CCL7; D002633:Chemotaxis / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines; D003609:Dactinomycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D004731:Endotoxins / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D017270:Lipoprotein(a) / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D018945:Monocyte Chemoattractant Proteins / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D011112:Polymyxin B / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D014470:Umbilical Cord / Q000502:physiology
D001054:Apolipoproteins A; C515450:CCL7 protein, human; D054410:Chemokine CCL7; D017077:Culture Media, Conditioned; D016207:Cytokines; D004731:Endotoxins; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D003609:Dactinomycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003513:Cycloheximide; D011112:Polymyxin B