ArticleArteriosclerosis, thrombosis, and vascular biology2015
HIF-1α and PFKFB3 Mediate a Tight Relationship Between Proinflammatory Activation and Anerobic Metabolism in Atherosclerotic Macrophages.
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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 114 papers.
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114citing papers in PubMed
7.3field-weighted citation impact, top 2% of its field
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114 citing papers in PubMed, 183 citations in OpenAlex.
- ATP Inside and Out: Understanding Atherosclerosis Through Energy Metabolism and Purinergic Signaling.Journal of atherosclerosis and thrombosis · 2026Review
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- Glucose Metabolic Enzyme PFKFB3 in Cardiopulmonary Vascular Health and Disease.Circulation research · 2026Review
- Hypoxia-inducible factors link inflammation and lipid metabolism in atherosclerotic macrophages.Frontiers in cardiovascular medicine · 2026Review
- Identification of Hypoxia-Related Genes in Human Myocardial Infarction and Cancers.Cardiology · 2026Article
- Novel insights of ferroptosis in atherosclerosis progression.Frontiers in cell and developmental biology · 2026Review
- Macrophage polarization in ischemia-reperfusion injury: from molecular mechanisms to therapeutic strategies.Frontiers in immunology · 2026Review
- Metabolic licensing and restriction of innate immunity in the tumor microenvironment.Frontiers in immunology · 2026Review
- Acetylbinankadsurin A Decreases Macrophage Glycolysis and Pro-Inflammatory Phenotype Polarization via Inhibiting HIF-1α to Alleviate Hepatic Fibrosis in Mice.Molecules (Basel, Switzerland) · 2025Article
- Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies.Journal of advanced research · 2025Review
- Pyruvate Carboxylase in Macrophages Aggravates Atherosclerosis by Regulating Metabolism Reprogramming to Promote Inflammatory Responses Through the Hypoxia-Inducible Factor-1 Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Macrophage energy metabolism in cardiometabolic disease.Molecular and cellular biochemistry · 2025Review
- Functional transformation of macrophage mitochondria in cardiovascular diseases.Molecular and cellular biochemistry · 2025Review
- Metabolism in the tumor microenvironment: implications for pathogenesis and therapeutics.Frontiers in immunology · 2025Review
- Metabolic adaptation to acute metabolic stress via PFKFB3 upregulation in rodent beta cells.Frontiers in endocrinology · 2025Article
- Immunometabolic Effect of Nitric Oxide on Human Macrophages Challenged With the SARS-CoV2-Induced Cytokine Storm. A Fluxomic Approach.Advanced healthcare materials · 2025Article
- Metformin as a strategy against false positives inHeliyon · 2024Article
- Current and Emerging Approaches to Imaging Large Vessel Vasculitis.Circulation. Cardiovascular imaging · 2024Review
- Targeting Macrophage Polarization for Reinstating Homeostasis following Tissue Damage.International journal of molecular sciences · 2024Review
- Crosstalk between P2Y receptors and cyclooxygenase activity in inflammation and tissue repair.Purinergic signalling · 2024Review
54 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 1 institution in 2 countries.
Ahmed TawakolFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.). atawakol@partners.org lbosca@iib.uam.es.
Parmanand SinghFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
Marina MojenaFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
María Pimentel-SantillanaFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
Hamed EmamiFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
Megan MacNabbFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
James H F RuddFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
Jagat NarulaFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
José A EnriquezFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
Paqui G TravésFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
María Fernández-VelascoFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
Ramón BartronsFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
Paloma Martín-SanzFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
Zahi A FayadFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
Alberto TejedorFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.).
Lisardo BoscáFrom the Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston (A.T., P.S., H.E., M.M.); Cardiology Division, Weill Cornell Medical College, New York Presbyterian Hospital, NY (P.S.); Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Centro de Investigación en Red en Enfermedades Hepáticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain (M.M., M.P.-S., P.G.T., M.F.-V., P.M.-S., L.B.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (M.M., A.T.); Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom (J.H.F.R.); Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N., Z.A.F.); Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro, Madrid, Spain (J.A.E.); The Salk Institute for Biological Studies, La Jolla, CA (P.G.T.); Idipaz, Hospital Universitario La Paz, Madrid, Spain (M.F.-V.); and Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Barcelona, Spain (R.B.). atawakol@partners.org lbosca@iib.uam.es.
Cornell University · US
Funding
MR/PET Imaging of coronary atherosclerosisR01HL071021 · NHLBI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI FAYAD, ZAHI A. · 2002 to 2019
$7.8MCardiac MR and CT ResearchT32HL076136 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI NEILAN, TOMAS G · 2004 to 2019
$4.9MTheranostic HDL nanoparticles for inflammatory macrophages in atherosclerosisR01EB009638 · NIBIB · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FAYAD, ZAHI A. · 2009 to 2016
$4.6MNanoparticles for Molecular MRI of AtherosclerosisR01HL078667 · NHLBI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI FAYAD, ZAHI A. · 2004 to 2008
$2.5MEffect of Low Dose Methotrexate on Arterial Inflammation in HIVR01HL122177 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI TAWAKOL, AHMED A · 2014 to 2017
$1.2MBritish Heart Foundation FS/12/29/29463British Heart Foundation PG/09/083/27667NHLBI NIH HHS 5T32 HL076136NHLBI NIH HHS HHSN268201000045CNHLBI NIH HHS HL122177NHLBI NIH HHS R01 HL071021NHLBI NIH HHS R01 HL078667NHLBI NIH HHS T32 HL076136NIBIB NIH HHS R01 EB009638
Abstract
objectiveAlthough it is accepted that macrophage glycolysis is upregulated under hypoxic conditions, it is not known whether this is linked to a similar increase in macrophage proinflammatory activation and whether specific energy demands regulate cell viability in the atheromatous plaque. APPROACH AND
resultsWe studied the interplay between macrophage energy metabolism, polarization, and viability in the context of atherosclerosis. Cultured human and murine macrophages and an in vivo murine model of atherosclerosis were used to evaluate the mechanisms underlying metabolic and inflammatory activity of macrophages in the different atherosclerotic conditions analyzed. We observed that macrophage energetics and inflammatory activation are closely and linearly related, resulting in dynamic calibration of glycolysis to keep pace with inflammatory activity. In addition, we show that macrophage glycolysis and proinflammatory activation mainly depend on hypoxia-inducible factor and on its impact on glucose uptake, and on the expression of hexokinase II and ubiquitous 6-phosphofructo-2-kinase. As a consequence, hypoxia potentiates inflammation and glycolysis mainly via these pathways. Moreover, when macrophages' ability to increase glycolysis through 6-phosphofructo-2-kinase is experimentally attenuated, cell viability is reduced if subjected to proinflammatory or hypoxic conditions, but unaffected under control conditions. In addition to this, granulocyte-macrophage colony-stimulating factor enhances anerobic glycolysis while exerting a mild proinflammatory activation.
conclusionsThese findings, in human and murine cells and in an animal model, show that hypoxia potentiates macrophage glycolytic flux in concert with a proportional upregulation of proinflammatory activity, in a manner that is dependent on both hypoxia-inducible factor -1α and 6-phosphofructo-2-kinase.
Indexed as
AnimalsAtherosclerosisCell HypoxiaDisease Models, AnimalGlycolysisHumansHypoxia-Inducible Factor 1, alpha SubunitInflammationMacrophagesMicePhosphofructokinase-2Tumor Necrosis Factor-alphaHypoxia-Inducible Factor 1, alpha SubunitPhosphofructokinase-2Tumor Necrosis Factor-alphaanoxiaatherosclerosisenergy metabolismmacrophagespositron-emission tomography
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