title: Fatty Acid binding protein 4 is associated with carotid atherosclerosis and outcome in patients with acute ischemic stroke.
abstract: OBJECTIVE
  Fatty acid binding protein 4 (FABP4) has been shown to play an important role in macrophage cholesterol trafficking and associated inflammation. To further elucidate the role of FABP4 in atherogenesis in humans, we examined the regulation of FABP4 in carotid atherosclerosis and ischemic stroke.
  
  
  METHODS
  We examined plasma FABP4 levels in asymptomatic (n = 28) and symptomatic (n = 31) patients with carotid atherosclerosis, as well as in 202 subjects with acute ischemic stroke. In a subgroup of patients we also analysed the expression of FABP4 within the atherosclerotic lesion. In addition, we investigated the ability of different stimuli with relevance to atherosclerosis to regulate FABP4 expression in monocytes/macrophages.
  
  
  RESULTS
  FABP4 levels were higher in patients with carotid atherosclerosis, both systemically and within the atherosclerotic lesion, with particular high mRNA levels in carotid plaques from patients with the most recent symptoms. Immunostaining of carotid plaques localized FABP4 to macrophages, while activated platelets and oxidized LDL were potent stimuli for FABP4 expression in monocytes/macrophages in vitro. When measured at the time of acute ischemic stroke, high plasma levels of FABP4 were significantly associated with total and cardiovascular mortality during follow-up, although we did not find that addition of FABP4 to the fully adjusted multivariate model had an effect on the prognostic discrimination for all-cause mortality as assessed by c-statistics.
  
  
  CONCLUSIONS
  FABP4 is linked to atherogenesis, plaque instability and adverse outcome in patients with carotid atherosclerosis and acute ischemic stroke.
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. sverre.holm@rr-research.no
authors.forename: Sverre
authors.initials: S
authors.lastname: Holm
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Tuva B
authors.initials: TB
authors.lastname: Dahl
authors.forename: Annika E
authors.initials: AE
authors.lastname: Michelsen
authors.forename: Mona
authors.initials: M
authors.lastname: Skjelland
authors.forename: David
authors.initials: D
authors.lastname: Russell
authors.forename: Ståle H
authors.initials: SH
authors.lastname: Nymo
authors.forename: Kirsten
authors.initials: K
authors.lastname: Krohg-Sørensen
authors.forename: Ole Petter
authors.initials: OP
authors.lastname: Clausen
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Jesper K
authors.initials: JK
authors.lastname: Jensen
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000097:blood / Q000150:complications* / Q000235:genetics; D016022:Case-Control Studies; D050556:Fatty Acid-Binding Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007511:Ischemia / Q000097:blood / Q000150:complications* / Q000235:genetics; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020521:Stroke / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein