title: Low-expression variant of fatty acid-binding protein 4 favors reduced manifestations of atherosclerotic disease and increased plaque stability.
abstract: BACKGROUND
  Fatty acid-binding protein 4 (FABP4 or aP2 in mice) has been identified as a key regulator of core aspects of cardiometabolic disorders, including lipotoxic endoplasmic reticulum stress in macrophages. A functional promoter polymorphism (rs77878271) of human FABP4 gene has been described resulting in reduced FABP4 transcription.
  
  
  RESULTS
  We investigated the effects of this low-expression variant of FABP4 on cardiovascular morbidity and carotid atherosclerosis on a population level (n=7491) and in patient cohorts representing endarterectomized patients with advanced carotid atherosclerosis (n=92) and myocardial infarction (n=3432). We found that the low-expression variant was associated with decreased total cholesterol levels (P=0.006) with the largest reduction in variant allele homozygotes. Obese variant allele carriers also showed reduced carotid intima-media thickness (P=0.010) and lower prevalence of carotid plaques (P=0.060). Consistently, the variant allele homozygotes showed 8-fold lower odds for myocardial infarction (P=0.019; odds ratio, 0.12; 95% confidence interval, 0.003-0.801). Within the carotid plaques, the variant allele was associated with a 3.8-fold reduction in FABP4 transcription (P=0.049) and 2.7-fold reduction in apoptosis (activated caspase 3; P=0.043). Furthermore, the variant allele was enriched to patients with asymptomatic carotid stenosis (P=0.038). High FABP4 expression in the carotid plaques was associated with lipid accumulation, intraplaque hemorrhages, plaque ulcerations, and phosphoactivated endoplasmic reticulum stress markers.
  
  
  CONCLUSIONS
  Our results reveal FABP4 rs77878271 as a novel variant affecting serum total cholesterol levels and cardiovascular risk. A therapeutic regimen reducing FABP4 expression within the atherosclerotic plaque may promote lesion stability through modulation of endoplasmic reticulum stress signaling, and attenuation of apoptosis, lipid burden, and inflammation.
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.). jani.saksi@helsinki.fi.
authors.forename: Jani
authors.initials: J
authors.lastname: Saksi
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Petra
authors.initials: P
authors.lastname: Ijäs
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Mäyränpää
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Krista
authors.initials: K
authors.lastname: Nuotio
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Pia M
authors.initials: PM
authors.lastname: Isoviita
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Jarno
authors.initials: J
authors.lastname: Tuimala
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Erno
authors.initials: E
authors.lastname: Lehtonen-Smeds
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Markku
authors.initials: M
authors.lastname: Kaste
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Antti
authors.initials: A
authors.lastname: Jula
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Juha
authors.initials: J
authors.lastname: Sinisalo
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Lokki
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Aki S
authors.initials: AS
authors.lastname: Havulinna
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.affiliation: From the Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (J.S., P.I., K.N., P.M.I., P.J.L.); HUSLAB, Division of Pathology (M.I.M.), Division of Cardiology, Department of Medicine (J.S., M.S.N.), Department of Neurology (P.I., K.N., M.K., P.J.L.), Helsinki University Central Hospital, Helsinki, Finland; Department of Pathology (M.I.M.), Transplantation Laboratory (M.-L.L.), Haartman Institute, Helsinki University, Helsinki, Finland; Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland (M.P., J.K.); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (P.J.L.); Finnish Red Cross Blood Service, Helsinki, Finland (J.T.); Wihuri Research Institute, Helsinki, Finland (E.L.-S., P.T.K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (A.J.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (A.J., M.P., A.S.H., V.S., J.K., M.J.); and The Estonian Genome Center, University of Tartu, Tartu, Estonia (M.P.).
authors.forename: Perttu J
authors.initials: PJ
authors.lastname: Lindsberg
mesh_terms: D000368:Aged; D000483:Alleles; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics; D002339:Carotid Arteries / Q000473:pathology; D004691:Endarterectomy; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000235:genetics*; D005260:Female; D005387:Finland; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007249:Inflammation / Q000097:blood; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D008055:Lipids
keywords: ER stress; FABP4 protein, human; apoptosis; atherosclerosis; carotid stenosis; cholesterol; coronary artery disease; genetics; stroke