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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

The Journal of clinical investigation, 2018-03, Vol.128 (3), p.1106-1124 [Periódico revisado por pares]

United States: American Society for Clinical Investigation

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Título:
CD163+ macrophages promote angiogenesis and vascular permeability accompanied by inflammation in atherosclerosis
Autor: 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
Assuntos: Adult ; Animals ; Antigens, CD - genetics ; Antigens, CD - metabolism ; Antigens, Differentiation, Myelomonocytic - genetics ; Antigens, Differentiation, Myelomonocytic - metabolism ; Atherosclerosis - metabolism ; Coronary Disease - metabolism ; Coronary Vessels - metabolism ; Disease Progression ; Female ; Hemoglobins - metabolism ; Humans ; Inflammation - metabolism ; Macrophages - cytology ; Macrophages - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Myocardial Infarction - metabolism ; Neovascularization, Pathologic ; Oxidative Stress ; Permeability ; Phenotype ; Polymorphism, Single Nucleotide ; Receptors, Cell Surface - genetics ; Receptors, Cell Surface - metabolism ; Signal Transduction
É parte de: The Journal of clinical investigation, 2018-03, Vol.128 (3), p.1106-1124
Descrição: 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.
Editor: United States: American Society for Clinical Investigation
Idioma: Inglês

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CD163+ macrophages promote angiogenesis and vascular permeability accompanied by inflammation in atherosclerosis

United States: American Society for Clinical Investigation

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