title: An imbalance between CD36 and ABCA1 protein expression favors lipid accumulation in stroke-prone ulcerated carotid plaques.
abstract: BACKGROUND
  CD36 is a macrophage scavenger receptor mediating the uptake of modified lipoproteins, whereas the ABCA1 transporter counteracts this effect by mediating cellular lipid efflux. Based on a DNA microarray, we previously found that the CD36 and ABCA1 genes were overexpressed in symptom-causing carotid plaques (CP) compared with nonsymptom-causing CP. To evaluate their role in CP destabilization, we conducted detailed immunohistochemical studies on the localization of lipids, CD36 and ABCA1 proteins, extravasated red blood cells, and atheromatous/necrotic tissue.
  
  
  METHODS
  Ninety-two high-grade (>70%) stenosing CP obtained from carotid endarterectomy were Oil-red-O-stained for evaluation of neutral lipids. Subgroups of nonsymptom-causing and symptom-causing CP (n=42) were further analyzed by immunostaining adjacent histological sections against CD36 and ABCA1 and examining them microscopically.
  
  
  RESULTS
  When compared with nonsymptom-causing CP, the amount of extracellular lipid and the expression of CD36 protein were elevated in symptom-causing CP, but no difference was found in ABCA1 expression. These observations were also confirmed when ulcerated and nonulcerated CP were compared. In ulcerated CP, CD36 protein expression was higher than that of ABCA1, and the opposite was true in nonulcerated CP. CD36 colocalized with extravasated red blood cells and atheromatous or necrotic areas in the various types of CP.
  
  
  CONCLUSIONS
  Our results suggest that an imbalance between lipid influx (CD36) and efflux (ABCA1) favors lipid accumulation in macrophages of ulcerated CP, thus contributing to plaque destabilization. Furthermore, colocalization of CD36 protein with red blood cells suggests that intraplaque hemorrhages may contribute to the lipid load and thus the stability of CP.
authors.affiliation: Research Program of Molecular Neurology, Biomedicum Helsinki, Helsinki, Finland. pia.isoviita@helsinki.fi
authors.forename: Pia M
authors.initials: PM
authors.lastname: Isoviita
authors.forename: Krista
authors.initials: K
authors.lastname: Nuotio
authors.forename: Jani
authors.initials: J
authors.lastname: Saksi
authors.forename: Riitta
authors.initials: R
authors.lastname: Turunen
authors.forename: Petra
authors.initials: P
authors.lastname: Ijäs
authors.forename: Janne
authors.initials: J
authors.lastname: Pitkäniemi
authors.forename: Lauri
authors.initials: L
authors.lastname: Soinne
authors.forename: Markku
authors.initials: M
authors.lastname: Kaste
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Perttu J
authors.initials: PJ
authors.lastname: Lindsberg
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000097:blood*; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D018955:CD36 Antigens / Q000032:analysis / Q000097:blood*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016893:Carotid Stenosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism / Q000502:physiology*; D052439:Lipid Metabolism Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D018955:CD36 Antigens