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CD163+ macrophages promote angiogenesis and vascular permeability accompanied by inflammation in atherosclerosis.
Guo, Liang; Akahori, Hirokuni; Harari, Emanuel; Smith, Samantha L; Polavarapu, Rohini; Karmali, Vinit; Otsuka, Fumiyuki; Gannon, Rachel L; Braumann, Ryan E; Dickinson, Megan H; Gupta, Anuj; Jenkins, Audrey L; Lipinski, Michael J; Kim, Johoon; Chhour, Peter; de Vries, Paul S; Jinnouchi, Hiroyuki; Kutys, Robert; Mori, Hiroyoshi; Kutyna, Matthew D; Torii, Sho; Sakamoto, Atsushi; Choi, Cheol Ung; Cheng, Qi; Grove, Megan L; Sawan, Mariem A; Zhang, Yin; Cao, Yihai; Kolodgie, Frank D; Cormode, David P; Arking, Dan E; Boerwinkle, Eric; Morrison, Alanna C; Erdmann, Jeanette; Sotoodehnia, Nona; Virmani, Renu; Finn, Aloke V.
Afiliación
  • Guo L; CVPath Institute, Gaithersburg, Maryland, USA.
  • Akahori H; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
  • Harari E; CVPath Institute, Gaithersburg, Maryland, USA.
  • Smith SL; CVPath Institute, Gaithersburg, Maryland, USA.
  • Polavarapu R; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
  • Karmali V; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
  • Otsuka F; CVPath Institute, Gaithersburg, Maryland, USA.
  • Gannon RL; CVPath Institute, Gaithersburg, Maryland, USA.
  • Braumann RE; CVPath Institute, Gaithersburg, Maryland, USA.
  • Dickinson MH; CVPath Institute, Gaithersburg, Maryland, USA.
  • Gupta A; Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Jenkins AL; MedStar Heart and Vascular Institute and MedStar Health Research Institute, MedStar Washington Hospital Center, Washington, DC, USA.
  • Lipinski MJ; MedStar Heart and Vascular Institute and MedStar Health Research Institute, MedStar Washington Hospital Center, Washington, DC, USA.
  • Kim J; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Chhour P; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • de Vries PS; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
  • Jinnouchi H; CVPath Institute, Gaithersburg, Maryland, USA.
  • Kutys R; CVPath Institute, Gaithersburg, Maryland, USA.
  • Mori H; CVPath Institute, Gaithersburg, Maryland, USA.
  • Kutyna MD; CVPath Institute, Gaithersburg, Maryland, USA.
  • Torii S; CVPath Institute, Gaithersburg, Maryland, USA.
  • Sakamoto A; CVPath Institute, Gaithersburg, Maryland, USA.
  • Choi CU; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
  • Cheng Q; CVPath Institute, Gaithersburg, Maryland, USA.
  • Grove ML; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
  • Sawan MA; Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Zhang Y; Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
  • Cao Y; Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
  • Kolodgie FD; CVPath Institute, Gaithersburg, Maryland, USA.
  • Cormode DP; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Arking DE; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Boerwinkle E; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
  • Morrison AC; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
  • Erdmann J; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
  • Sotoodehnia N; Institute for Cardiogenetics, University of Lübeck, and German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Germany.
  • Virmani R; Division of Cardiology, Department of Medicine and Epidemiology, Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.
  • Finn AV; CVPath Institute, Gaithersburg, Maryland, USA.
J Clin Invest ; 128(3): 1106-1124, 2018 03 01.
Article en En | MEDLINE | ID: mdl-29457790
Intake of hemoglobin by the hemoglobin-haptoglobin receptor CD163 leads to a distinct alternative non-foam cell antiinflammatory macrophage phenotype that was previously considered atheroprotective. Here, we reveal an unexpected but important pathogenic role for these macrophages in atherosclerosis. Using human atherosclerotic samples, cultured cells, and a mouse model of advanced atherosclerosis, we investigated the role of intraplaque hemorrhage on macrophage function with respect to angiogenesis, vascular permeability, inflammation, and plaque progression. In human atherosclerotic lesions, CD163+ macrophages were associated with plaque progression, microvascularity, and a high level of HIF1α and VEGF-A expression. We observed irregular vascular endothelial cadherin in intraplaque microvessels surrounded by CD163+ macrophages. Within these cells, activation of HIF1α via inhibition of prolyl hydroxylases promoted VEGF-mediated increases in intraplaque angiogenesis, vascular permeability, and inflammatory cell recruitment. CD163+ macrophages increased intraplaque endothelial VCAM expression and plaque inflammation. Subjects with homozygous minor alleles of the SNP rs7136716 had elevated microvessel density, increased expression of CD163 in ruptured coronary plaques, and a higher risk of myocardial infarction and coronary heart disease in population cohorts. Thus, our findings highlight a nonlipid-driven mechanism by which alternative macrophages promote plaque angiogenesis, leakiness, inflammation, and progression via the CD163/HIF1α/VEGF-A pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos de Diferenciación Mielomonocítica / Antígenos CD / Receptores de Superficie Celular / Aterosclerosis / Inflamación / Macrófagos / Neovascularización Patológica Tipo de estudio: Prognostic_studies Límite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Invest Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos de Diferenciación Mielomonocítica / Antígenos CD / Receptores de Superficie Celular / Aterosclerosis / Inflamación / Macrófagos / Neovascularización Patológica Tipo de estudio: Prognostic_studies Límite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Invest Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos