title: Oleic acid induces smooth muscle foam cell formation and enhances atherosclerotic lesion development via CD36.
abstract: BACKGROUND
  Elevated plasma free fatty acid (FFA) levels have been linked to the development of atherosclerosis. However, how FFA causes atherosclerosis has not been determined. Because fatty acid translocase (FAT/CD36) is responsible for the uptake of FFA, we hypothesized that the atherogenic effects of FFA may be mediated via CD36.
  
  
  RESULTS
  We tested this hypothesis using cultured rat aortic smooth muscle cells (SMCs) treated with oleic acid (OA). We found that OA induces lipid accumulation in SMCs in a dose dependent manner. Rat aortic SMCs treated for 48 hours with OA (250 μmol/L) became foam cells based on morphological (Oil Red O staining) and biochemical (5 times increase in cellular triglyceride) criteria. Moreover, specific inhibition of CD36 by sulfo-N-succinimidyl oleate significantly attenuated OA induced lipid accumulation and foam cell formation. To confirm these results in vivo, we used ApoE-deficient mice fed with normal chow (NC), OA diet, NC plus lipolysis inhibitor acipimox or OA plus acipimox. OA-fed mice showed increased plasma FFA levels and enhanced atherosclerotic lesions in the aortic sinus compared to the NC group (both p < 0.01). This effect was partially reversed by acipimox (lesion area: OA: 3.09 ± 0.10 ×10(5) μm(2) vs. OA plus acipimox: 2.60 ± 0.10 ×10(5) μm(2), p < 0.05; FFA: OA: 0.91 ± 0.03 mmol/L vs. OA plus acipimox: 0.78 ± 0.03 mmol/L, p < 0.05).
  
  
  CONCLUSIONS
  These findings suggest that OA induces smooth muscle foam cell formation and enhances atherosclerotic lesions in part though CD36. Furthermore, these findings provide a novel model for the investigation of atherosclerosis.
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, PR China.
authors.forename: Shuangtao
authors.initials: S
authors.lastname: Ma
authors.forename: Dachun
authors.initials: D
authors.lastname: Yang
authors.forename: De
authors.initials: D
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Tang
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000139:chemically induced* / Q000378:metabolism; D015153:Blotting, Western; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005487:Foam Cells / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects*; D019301:Oleic Acid / Q000494:pharmacology*; D058226:Plaque, Atherosclerotic / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001057:Apolipoproteins E; D018955:CD36 Antigens; D019301:Oleic Acid