title: Apolipoprotein(a) induces monocyte chemotactic activity in human vascular endothelial cells.
abstract: BACKGROUND
  Elevated levels of lipoprotein(a) [Lp(a)] are associated with premature atherosclerosis; however, the mechanisms are not known. Recruitment of monocytes to the blood vessel wall is an early event in atherogenesis.
  
  
  RESULTS
  This study has found that unoxidized Lp(a) induced human umbilical vein endothelial cells (HUVECs) to secrete monocyte chemotactic activity (MCA), whereas LDL under the same conditions did not. In the absence of HUVECs, Lp(a) had no direct MCA. Endotoxin was shown not to be responsible for the induction of MCA. Actinomycin D and cycloheximide inhibited the HUVEC response to Lp(a), indicating that protein and RNA synthesis were required. The apolipoprotein(a) [apo(a)] portion of Lp(a) was identified as the structural component of Lp(a) responsible for inducing MCA. Lp(a) and apo(a) also stimulated human coronary artery endothelial cells to produce MCA. Granulocyte-monocyte colony-stimulating factor (GM-CSF) antigen was not detected in the Lp(a)-conditioned medium, nor was monocyte chemoattractant protein-1 mRNA induced in HUVECs by Lp(a).
  
  
  CONCLUSIONS
  These findings suggest that Lp(a) may be involved in the recruitment of monocytes to the vessel wall and provide a novel mechanism for the participation of Lp(a) in the atherogenic process.
authors.affiliation: Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029, USA. mpoon@smtplink.mssm.edu
authors.forename: M
authors.initials: M
authors.lastname: Poon
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: K G
authors.initials: KG
authors.lastname: Dunsky
authors.forename: M B
authors.initials: MB
authors.lastname: Taubman
authors.forename: P C
authors.initials: PC
authors.lastname: Harpel
mesh_terms: D001053:Apolipoproteins / Q000378:metabolism*; D053241:Apoprotein(a); D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D017270:Lipoprotein(a) / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010641:Phenotype; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis
chemical_list: D001053:Apolipoproteins; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D018945:Monocyte Chemoattractant Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003513:Cycloheximide; D053241:Apoprotein(a)