ArticleArteriosclerosis, thrombosis, and vascular biology2017
Mechanical Activation of Hypoxia-Inducible Factor 1α Drives Endothelial Dysfunction at Atheroprone Sites.
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Article in Arteriosclerosis, thrombosis, and vascular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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121citing papers in PubMed
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121 citing papers in PubMed, 202 citations in OpenAlex.
- Glycohypoxia: a hypothesis linking chronic hyperglycemia to functional hypoxia and diabetic complications in type 2 diabetes.Medical gas research · 2026Review
- ATP Inside and Out: Understanding Atherosclerosis Through Energy Metabolism and Purinergic Signaling.Journal of atherosclerosis and thrombosis · 2026Review
- YTHDF3 promotes angiogenesis in endometriosis by enhancing the translation efficiency of PFKFB3.Angiogenesis · 2026Article
- Impaired Glycolysis Leads to Defective Efferocytosis and Impaired Plaque Resolution inCirculation · 2026Article
- Carotid body hypoxia induces angiogenesis and correlates with glomic artery anatomy and carotid artery atherosclerosis.iScience · 2026Article
- Substrate stiffness regulates HIF-1α signalling via β1-integrin/myosin-2/NF-κB axis.Journal of translational medicine · 2026Article
- Purine metabolic adaptation protects the endothelium from disturbed flow-induced DNA damage and atherosclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Brain endothelial PTPRO drives LPS-induced metabolic reprogramming and neuroinflammation in sepsis-associated encephalopathy.Journal of neuroinflammation · 2026Article
- Advances in the Research of Hypoxia-Inducible Factor-1Alpha and Plasminogen Activator Inhibitor-1 in Vascular-Related Diseases.Journal of clinical medicine research · 2026Review
- Ginsenoside Re regulates PFKFB3-mediated glycolysis to inhibit endothelial cell migration to ameliorate atherosclerosis.Journal of ginseng research · 2026Article
- The Emerging Role of Mechanobiology in Connecting Metabolic and Cardiovascular Diseases: From Fundamentals to Future Therapies.Biomedicines · 2026Review
- Hypoxia-Inducible Factor 1-α in Autoimmune Diseases-Insights from the Paradigm of Hashimoto's Thyroiditis: A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- Narciclasine Alleviates Endothelial Inflammation and Atherosclerosis Initiation by Inhibiting Histone Lactylation-Mediated NF-κB Activation.Inflammation · 2026Article
- Endothelial KSR2 regulated by genetic variation protects against atherosclerosis through AMPKα1 stabilization.Theranostics · 2026Article
- Endothelial Metabolic Reprogramming Links Diabetes to Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Impacts of aging and fluid shear stress on vascular endothelial metabolism and atherosclerosis development.Journal of biomedical science · 2025Review
- Adiponectin mediated metabolic and sphingolipid alterations in preventing endothelial dysfunction.Molecular and cellular biochemistry · 2025Article
- Oxygen Sensing in Osteocytes: From Physiology to Age-related Osteoporosis.Current osteoporosis reports · 2025Review
- Fluid Shear Stress-Regulated Vascular Remodeling: Past, Present, and Future.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Endothelial c-REL orchestrates atherosclerosis at regions of disturbed flow through crosstalk with TXNIP-p38 and non-canonical NF-κB pathways.Cardiovascular research · 2025Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 2 institutions in 1 country.
Shuang FengFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Neil BowdenFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Maria FragiadakiFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Celine SouilholFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Sarah HsiaoFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Marwa MahmoudFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Scott AllenFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Daniela PirriFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Blanca Tardajos AyllonFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Shamima AkhtarFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
A A Roger ThompsonFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Hanjoong JoFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Christian WeberFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Victoria RidgerFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Andreas SchoberFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).
Paul C EvansFrom the Department of Infection, Immunity, and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre (S.F., N.B., M.F., C.S., H.S., M.M., D.P., B.T.A., A.A.R.T., V.R., P.C.E.) and Sheffield Institute for Translational Neuroscience (S.A.), University of Sheffield, United Kingdom; Institute for Cardiovascular Prevention, Ludwig-Maximilians University of Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (S.A., C.W., A.S.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.). paul.evans@sheffield.ac.uk.
German Centre for Cardiovascular Research · DELudwig-Maximilians-Universität München · DE
Funding
T cell triggering events and hypertensionP01HL095070 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG · 2009 to 2019
$20.5MAutologous Cardiomyocytes from Masseter Muscles to Repair Myocardial InfarctionR56HL130042 · NHLBI · UNIVERSITY OF CINCINNATI · PI WANG, YIGANG · 2016 to 2016
$473kBritish Heart Foundation FS/13/27/30191British Heart Foundation PG/09/088/28058British Heart Foundation RG/13/1/30042Medical Research Council G0802255NHLBI NIH HHS P01 HL095070
Abstract
objectiveAtherosclerosis develops near branches and bends of arteries that are exposed to low shear stress (mechanical drag). These sites are characterized by excessive endothelial cell (EC) proliferation and inflammation that promote lesion initiation. The transcription factor HIF1α (hypoxia-inducible factor 1α) is canonically activated by hypoxia and has a role in plaque neovascularization. We studied the influence of shear stress on HIF1α activation and the contribution of this noncanonical pathway to lesion initiation. APPROACH AND
resultsQuantitative polymerase chain reaction and en face staining revealed that HIF1α was expressed preferentially at low shear stress regions of porcine and murine arteries. Low shear stress induced HIF1α in cultured EC in the presence of atmospheric oxygen. The mechanism involves the transcription factor nuclear factor-κB that induced HIF1α transcripts and induction of the deubiquitinating enzyme Cezanne that stabilized HIF1α protein. Gene silencing revealed that HIF1α enhanced proliferation and inflammatory activation in EC exposed to low shear stress via induction of glycolysis enzymes. We validated this observation by imposing low shear stress in murine carotid arteries (partial ligation) that upregulated the expression of HIF1α, glycolysis enzymes, and inflammatory genes and enhanced EC proliferation. EC-specific genetic deletion of HIF1α in hypercholesterolemic apolipoprotein E-defecient mice reduced inflammation and endothelial proliferation in partially ligated arteries, indicating that HIF1α drives inflammation and vascular dysfunction at low shear stress regions.
conclusionsMechanical low shear stress activates HIF1α at atheroprone regions of arteries via nuclear factor-κB and Cezanne. HIF1α promotes atherosclerosis initiation at these sites by inducing excessive EC proliferation and inflammation via the induction of glycolysis enzymes.
Indexed as
Mechanotransduction, CellularPlaque, AtheroscleroticAnimalsApolipoproteins EAtherosclerosisCell ProliferationCells, CulturedDeubiquitinating EnzymesDisease Models, AnimalEndopeptidasesEndothelial CellsEnzyme InductionFemaleGenetic Predisposition to DiseaseGlycolysisHumansApolipoproteins EDeubiquitinating EnzymesEndopeptidasesHIF1A protein, humanHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitInflammation MediatorsNF-kappa BOtud7b protein, mouseOxygenapolipoproteins Eatherosclerosisendothelial cellsglycolysishypoxia-inducible factor 1
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