title: Expression of fatty acid-binding protein 4/aP2 is correlated with plaque instability in carotid atherosclerosis.
abstract: OBJECTIVE
  the molecular basis for atherosclerotic plaque vulnerability with high risk of plaque rupture and thromboembolism is complex. We investigated whether clinical estimates of plaque stability correlate with differentially expressed mRNA transcripts within the lesion.
  
  
  RESULTS
  endarterectomy samples from patients undergoing surgery for symptomatic and asymptomatic carotid stenosis were prospectively collected and clinical parameters recorded in the Biobank of Karolinska Carotid Endarterectomies. mRNA expression profiling (n = 40) and quantitative RT-PCR (n = 105) revealed increased levels of fatty acid-binding protein 4 (FABP4/aP2) in lesions from patients with recent symptoms of plaque instability compared to asymptomatic patients (array: FC = 2, P < 0.05; RT-PCR: P < 0.05). At the mRNA level, FABP4/aP2 correlated with the cell markers CD36, CD68 and CD163 of monocyte/macrophage lineage as well as with CD4-positive T cells. FABP4/aP2 mRNA expression was also correlated with enzymes of the leukotriene pathway, 5-lipoxygenase and leukotriene A4 hydrolase. In addition, analysis of transcript profiles identified CD52 and adipophilin as the mRNAs with the highest correlation with FABP4/aP2. Expression of FABP4/aP2 by macrophages and CD52 by T cells in the lesion was confirmed by immunohistochemistry.
  
  
  CONCLUSIONS
  expression of FABP4/aP2 is increased at the mRNA level in unstable carotid plaques. Immunohistochemical analyses showed localization of FABP4/aP2 to macrophage populations. These FABP4/aP2-positive macrophages constitute an important and prevalent phenotype and could provide a new link between scavenging-mediated lipid uptake and cellular metabolic stress in plaque. In addition FABP4/aP2 correlates with other important signs of inflammation and plaque instability, such as T cells and leukotriene enzymes. Taken together, these results indicate that FABP4/aP2 is a key factor connecting vascular and cellular lipid accumulation to inflammation.
authors.affiliation: Department of Medicine, Experimental Cardiovascular Research, Karolinska Institutet Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: H E
authors.initials: HE
authors.lastname: Agardh
authors.forename: L
authors.initials: L
authors.lastname: Folkersen
authors.forename: J
authors.initials: J
authors.lastname: Ekstrand
authors.forename: D
authors.initials: D
authors.lastname: Marcus
authors.forename: J
authors.initials: J
authors.lastname: Swedenborg
authors.forename: U
authors.initials: U
authors.lastname: Hedin
authors.forename: A
authors.initials: A
authors.lastname: Gabrielsen
authors.forename: G
authors.initials: G
authors.lastname: Paulsson-Berne
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D000074301:CD52 Antigen; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000601:surgery; D016894:Endarterectomy, Carotid; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000601:surgery; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015415:Biomarkers; D000074301:CD52 Antigen; C000613862:CD52 protein, human; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D006023:Glycoproteins; D012333:RNA, Messenger