ArticleArteriosclerosis, thrombosis, and vascular biology2015
Deficiency of HIF1α in Antigen-Presenting Cells Aggravates Atherosclerosis and Type 1 T-Helper Cell Responses in Mice.
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Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31citing papers in PubMed
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31 citing papers in PubMed, 50 citations in OpenAlex.
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Myeloid HIF1α has only a minor impact on atherosclerosis development.Vascular biology (Bristol, England) · 2026Article
- The role of hypoxic microenvironment in rheumatoid arthritis.Frontiers in immunology · 2025Review
- Screening of key genes related to M6A methylation in patients with heart failure.BMC cardiovascular disorders · 2024Article
- Spatial multiomics atlas reveals smooth muscle phenotypic transformation and metabolic reprogramming in diabetic macroangiopathy.Cardiovascular diabetology · 2024Article
- Unraveling the Roles of HIF-1, HO-1, GLUT-1 and GLUT-4 in Myocardial Protection.International journal of drug discovery and pharmacology · 2024Article
- The Evolving Role of Dendritic Cells in Atherosclerosis.International journal of molecular sciences · 2024Review
- The role of hypoxic microenvironment in autoimmune diseases.Frontiers in immunology · 2024Review
- Screening of potential regulatory genes in carotid atherosclerosis vascular immune microenvironment.PloS one · 2024Article
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Article
- Deficiency of myeloid PHD proteins aggravates atherogenesis via macrophage apoptosis and paracrine fibrotic signalling.Cardiovascular research · 2022Article
- Emerging role of hypoxia-inducible factor-1α in inflammatory autoimmune diseases: A comprehensive review.Frontiers in immunology · 2022Review
- Cholesterol and HIF-1α: Dangerous Liaisons in Atherosclerosis.Frontiers in immunology · 2022Review
- Review
- Association of hypoxia and mitochondrial damage associated molecular patterns in the pathogenesis of vein graft failure: a pilot study.Translational research : the journal of laboratory and clinical medicine · 2021Article
- Myeloid Cell Diversity and Impact of Metabolic Cues during Atherosclerosis.Immunometabolism · 2020Article
- Role of dendritic cell metabolic reprogramming in tumor immune evasion.International immunology · 2020Review
- The Research Progress of Vascular Macrophages and Atherosclerosis.Oxidative medicine and cellular longevity · 2020Review
- Immunobiology of Atherosclerosis: A Complex Net of Interactions.International journal of molecular sciences · 2019Review
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Authors and funding
16 authors at 3 institutions in 2 countries.
Sweena M ChaudhariFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Judith C SluimerFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Miriam KochFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Thomas L TheelenFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Helga D MantheyFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Martin BuschFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Celia Caballero-FrancoFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Frederick VogelFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Clément CochainFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Jaroslav PelisekFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Mat J DaemenFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Manfred B LutzFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Agnes GörlachFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Stephan KisslerFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Heike M HermannsFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.).
Alma ZerneckeFrom the Institute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg (S.M.C., M.K., C.C., A.Z.), Rudolf Virchow Center (H.D.M., M.B., H.M.H.), Institute of Virology and Immunobiology (M.B.L.), and Division of Hepatology, Medical Clinic II, University Hospital Würzburg (H.M.H.), University of Würzburg, Würzburg, Germany; Department of Pathology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands (J.C.S., T.L.T.); Joslin Diabetes Center, Harvard Medical School, Boston, MA (C.C.-F., S.K.); Experimental and Molecular Pediatric Cardiology, German Heart Center Munich, TU Munich, Munich, Germany (F.V., A.G.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany (J.P.); and Department of Pathology, Amsterdam Medical Centre, Amsterdam, The Netherlands (M.J.D.). alma.zernecke@uni-wuerzburg.de.
Deutsches Herzzentrum München · DEJoslin Diabetes Center · USHarvard University · US
Funding
SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI JEAN E. SCHAFFER · 1986 to 2026
$50.5MNIDDK NIH HHS P30 DK036836NIDDK NIH HHS P30DK036836
Abstract
objectiveAlthough immune responses drive the pathogenesis of atherosclerosis, mechanisms that control antigen-presenting cell (APC)-mediated immune activation in atherosclerosis remain elusive. We here investigated the function of hypoxia-inducible factor (HIF)-1α in APCs in atherosclerosis. APPROACH AND
resultsWe found upregulated HIF1α expression in CD11c(+) APCs within atherosclerotic plaques of low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice. Conditional deletion of Hif1a in CD11c(+) APCs in high-fat diet-fed Ldlr(-/-) mice accelerated atherosclerotic plaque formation and increased lesional T-cell infiltrates, revealing a protective role of this transcription factor. HIF1α directly controls Signal Transducers and Activators of Transcription 3 (Stat3), and a reduced STAT3 expression was found in HIF1α-deficient APCs and aortic tissue, together with an upregulated interleukin-12 expression and expansion of type 1 T-helper (Th1) cells. Overexpression of STAT3 in Hif1a-deficient APCs in bone marrow reversed enhanced atherosclerotic lesion formation and reduced Th1 cell expansion in chimeric Ldlr(-/-) mice. Notably, deletion of Hif1a in LysM(+) bone marrow cells in Ldlr(-/-) mice did not affect lesion formation or T-cell activation. In human atherosclerotic lesions, HIF1α, STAT3, and interleukin-12 protein were found to colocalize with APCs.
conclusionsOur findings identify HIF1α to antagonize APC activation and Th1 T cell polarization during atherogenesis in Ldlr(-/-) mice and to attenuate the progression of atherosclerosis. These data substantiate the critical role of APCs in controlling immune mechanisms that drive atherosclerotic lesion development.
Indexed as
AnimalsAntigen-Presenting CellsAortaAortic DiseasesAtherosclerosisCarotid Artery DiseasesCD11c AntigenCells, CulturedCoculture TechniquesDiet, High-FatDisease Models, AnimalHumansHypoxia-Inducible Factor 1, alpha SubunitInterleukin-12Lymphocyte ActivationMacrophagesCD11c AntigenHIF1A protein, humanHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitInterleukin-12Receptors, LDLSTAT3 protein, humanStat3 protein, mouseSTAT3 Transcription Factorantigen-presenting cellsatherosclerosisdiethigh-fatinflammationleukocytes
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