title: Fatty acids cause alterations of human arterial smooth muscle cell proteoglycans that increase the affinity for low-density lipoprotein.
abstract: OBJECTIVE
  The dyslipidemia of insulin resistance, with high levels of albumin-bound fatty acids, is a strong cardiovascular disease risk. Human arterial smooth muscle cell (hASMC) matrix proteoglycans (PGs) contribute to the retention of apoB lipoproteins in the intima, a possible key step in atherogenesis. We investigated the effects of high NEFA levels on the PGs secreted by hASMCs and whether these effects might alter the PG affinity for low-density lipoprotein.
  
  
  RESULTS
  hASMC exposed for 72 hours to high concentrations (800 micromol/L) of linoleate (LO) or palmitate upregulated the core protein mRNAs of the major PGs, as measured by quantitative PCR. Insulin (1 nmol/L) and the PPARgamma agonist rosiglitazone (10 micromol/L) blocked these effects. In addition, high LO increased the mRNA levels of enzymes required for glycosaminoglycan (GAG) synthesis. Exposure to NEFA increased the chondroitin sulfate:heparan sulfate ratio and the negative charge of the PGs. Because of these changes, the GAGs secreted by LO-treated cells had a higher affinity for human low-density lipoprotein than GAGs from control cells. Insulin and rosiglitazone inhibited this increase in affinity.
  
  
  CONCLUSIONS
  The response of hASMC to NEFA could induce extracellular matrix alterations favoring apoB lipoprotein deposition and atherogenesis.
authors.affiliation: Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy at Göteborg University, 413 45 Gothenburg, Sweden.
authors.forename: Mariam
authors.initials: M
authors.lastname: Rodríguez-Lee
authors.forename: Gunnel
authors.initials: G
authors.lastname: Ostergren-Lundén
authors.forename: Boel
authors.initials: B
authors.lastname: Wallin
authors.forename: Jonatan
authors.initials: J
authors.lastname: Moses
authors.forename: Göran
authors.initials: G
authors.lastname: Bondjers
authors.forename: Germán
authors.initials: G
authors.lastname: Camejo
mesh_terms: D001158:Arteries / Q000166:cytology; D050197:Atherosclerosis / Q000378:metabolism*; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D050171:Dyslipidemias / Q000378:metabolism; D016695:Glycosyltransferases / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D019787:Linoleic Acid / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D053675:Versicans
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D007004:Hypoglycemic Agents; D007328:Insulin; D037181:Lectins, C-Type; D008077:Lipoproteins, LDL; D010168:Palmitates; D011509:Proteoglycans; D012333:RNA, Messenger; D013431:Sulfates; D014280:Triglycerides; C508322:VCAN protein, human; D053675:Versicans; D019787:Linoleic Acid; D016695:Glycosyltransferases; D015238:Sulfotransferases