title: Reversal of hypoxia in murine atherosclerosis prevents necrotic core expansion by enhancing efferocytosis.
abstract: OBJECTIVE
  Advanced murine and human plaques are hypoxic, but it remains unclear whether plaque hypoxia is causally related to atherogenesis. Here, we test the hypothesis that reversal of hypoxia in atherosclerotic plaques by breathing hyperoxic carbogen gas will prevent atherosclerosis.
  
  
  RESULTS
  Low-density lipoprotein receptor-deficient mice (LDLR(-/-)) were fed a Western-type diet, exposed to carbogen (95% O2, 5% CO2) or air, and the effect on plaque hypoxia, size, and phenotype was studied. First, the hypoxic marker pimonidazole was detected in murine LDLR(-/-) plaque macrophages from plaque initiation onwards. Second, the efficacy of breathing carbogen (90 minutes, single exposure) was studied. Compared with air, carbogen increased arterial blood pO2 5-fold in LDLR(-/-) mice and reduced plaque hypoxia in advanced plaques of the aortic root (-32%) and arch (-84%). Finally, the effect of repeated carbogen exposure on progression of atherosclerosis was studied in LDLR(-/-) mice fed a Western-type diet for an initial 4 weeks, followed by 4 weeks of diet and carbogen or air (both 90 min/d). Carbogen reduced plaque hypoxia (-40%), necrotic core size (-37%), and TUNEL(+) (terminal uridine nick-end labeling positive) apoptotic cell content (-50%) and increased efferocytosis of apoptotic cells by cluster of differentiation 107b(+) (CD107b, MAC3) macrophages (+36%) in advanced plaques of the aortic root. Plaque size, plasma cholesterol, hematopoiesis, and systemic inflammation were unchanged. In vitro, hypoxia hampered efferocytosis by bone marrow-derived macrophages, which was dependent on the receptor Mer tyrosine kinase.
  
  
  CONCLUSIONS
  Carbogen restored murine plaque oxygenation and prevented necrotic core expansion by enhancing efferocytosis, likely via Mer tyrosine kinase. Thus, plaque hypoxia is causally related to necrotic core expansion.
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Elke
authors.initials: E
authors.lastname: Marsch
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Theelen
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Jasper A F
authors.initials: JA
authors.lastname: Demandt
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Mike
authors.initials: M
authors.lastname: Jeurissen
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Mathijs
authors.initials: M
authors.lastname: van Gink
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Robin
authors.initials: R
authors.lastname: Verjans
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Anique
authors.initials: A
authors.lastname: Janssen
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Jack P
authors.initials: JP
authors.lastname: Cleutjens
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Steven J R
authors.initials: SJ
authors.lastname: Meex
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Marjo M
authors.initials: MM
authors.lastname: Donners
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Guido R
authors.initials: GR
authors.lastname: Haenen
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Ludwig J
authors.initials: LJ
authors.lastname: Dubois
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Marion J
authors.initials: MJ
authors.lastname: Gijbels
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Johan W M
authors.initials: JW
authors.lastname: Heemskerk
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fisher
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Erik A L
authors.initials: EA
authors.lastname: Biessen
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Janssen
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.).
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
authors.affiliation: From the Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) (E.M., T.L.T., J.A.F.D., M.J., M.v.G., R.V., A.J., J.P.C., M.M.D., M.J.G., E.A.L.B., J.C.S.), Department of Clinical Chemistry (S.J.R.M.), Department of Toxicology (G.R.H.), Department of Internal Medicine, CARIM (C.G.S.), Department of Radiation Oncology (Maastro Lab), GROW (L.J.D., P.L.), Department of Molecular Genetics, CARIM (M.J.G.), Department of Biochemistry, CARIM (J.W.M.H.), Department of Pharmacology, CARIM (B.J.J.), Maastricht University Medical Centre, Maastricht, The Netherlands; Paris Centre de Recherche Cardiovasculaire (PARCC) Inserm-UMR 970, Paris, France (Z.M.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (Z.M.); Department of Medical Biochemistry (M.J.G.) and Department of Pathology (M.J.A.P.D.), AMC, Amsterdam, The Netherlands; and Department of Medicine (Cardiology), New York University School of Medicine, New York (E.A.F.). judith.sluimer@maastrichtuniversity.nl.
authors.forename: Judith C
authors.initials: JC
authors.lastname: Sluimer
mesh_terms: D000818:Animals; D017209:Apoptosis; D018955:CD36 Antigens / Q000172:deficiency / Q000235:genetics; D002245:Carbon Dioxide / Q000008:administration & dosage; D006801:Humans; D000860:Hypoxia / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis; D010100:Oxygen / Q000008:administration & dosage / Q000097:blood; D010587:Phagocytosis; D058226:Plaque, Atherosclerotic / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D000076202:c-Mer Tyrosine Kinase
chemical_list: D018955:CD36 Antigens; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D011973:Receptors, LDL; D002245:Carbon Dioxide; C011700:carbogen; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; D010100:Oxygen
keywords: atherosclerosis; carbogen; hypoxia; macrophages