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CD163+ Macrophages Induce Endothelial-to-Mesenchymal Transition in Atheroma.
Mori, Masayuki; Sakamoto, Atsushi; Kawakami, Rika; Guo, Liang; Slenders, Lotte; Mosquera, Jose Verdezoto; Ghosh, Saikat Kumar B; Wesseling, Marian; Shiraki, Tatsuya; Bellissard, Arielle; Shah, Palak; Weinkauf, Craig C; Konishi, Takao; Sato, Yu; Cornelissen, Anne; Kawai, Kenji; Jinnouchi, Hiroyuki; Xu, Weili; Vozenilek, Aimee E; Williams, Desiree; Tanaka, Takamasa; Sekimoto, Teruo; Kelly, Michael C; Fernandez, Raquel; Grogan, Alyssa; Coslet, A J; Fedotova, Alisa; Kurse, Anjali; Mokry, Michal; Romero, Maria E; Kolodgie, Frank D; Pasterkamp, Gerard; Miller, Clint L; Virmani, Renu; Finn, Aloke V.
Afiliação
  • Mori M; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Sakamoto A; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Kawakami R; Hamamatsu University School of Medicine, Shizuoka, Japan (A.S.).
  • Guo L; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Slenders L; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Mosquera JV; University Medical Center Utrecht, the Netherlands (L.S., M.W., M. Mokry, G.P.).
  • Ghosh SKB; Department of Public Health Sciences, Department of Biochemistry and Molecular Genetics, Center for Public Health Genomics, University of Virginia, Charlottesville (J.V.M., C.L.M.).
  • Wesseling M; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Shiraki T; University Medical Center Utrecht, the Netherlands (L.S., M.W., M. Mokry, G.P.).
  • Bellissard A; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Shah P; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Weinkauf CC; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Konishi T; The University of Arizona, Tucson (C.C.W.).
  • Sato Y; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Cornelissen A; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Kawai K; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Jinnouchi H; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Xu W; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Vozenilek AE; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Williams D; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Tanaka T; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Sekimoto T; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Kelly MC; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Fernandez R; Single Cell Analysis Facility, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD (M.C.K.).
  • Grogan A; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Coslet AJ; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Fedotova A; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Kurse A; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Mokry M; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Romero ME; University Medical Center Utrecht, the Netherlands (L.S., M.W., M. Mokry, G.P.).
  • Kolodgie FD; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Pasterkamp G; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Miller CL; Department of Pathology, CVPath Institute, Inc, Gaithersburg, MD (M. Mori, A.S., R.K., L.G., S.K.B.G., T. Shiraki, A.B., P.S., T.K., Y.S., A.C., K.K., H.J., W.X., A.E.V., D.W., T.T., T. Sekimoto, R.F., A.G., A.J.C., A.F., A.K., M.E.R., F.D.K., R.V., A.V.F.).
  • Virmani R; University Medical Center Utrecht, the Netherlands (L.S., M.W., M. Mokry, G.P.).
  • Finn AV; Department of Public Health Sciences, Department of Biochemistry and Molecular Genetics, Center for Public Health Genomics, University of Virginia, Charlottesville (J.V.M., C.L.M.).
Circ Res ; 135(2): e4-e23, 2024 Jul 05.
Article em En | MEDLINE | ID: mdl-38860377
ABSTRACT

BACKGROUND:

Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163+ macrophages. Here, we explored the hypothesis that CD163+ macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap.

METHODS:

Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone ApoE-/- and ApoE-/-/CD163-/- mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments.

RESULTS:

In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163+ macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL (terminal deoxynucleotidyl transferase-dUTP nick end labeling) positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa ß) signaling by proinflammatory cytokines released from CD163+ macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase-3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163+ macrophage-induced EndMT. Additionally, CD163 deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes.

CONCLUSIONS:

CD163+ macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antígenos de Diferenciação Mielomonocítica / Antígenos CD / Receptores de Superfície Celular / Placa Aterosclerótica / Macrófagos Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antígenos de Diferenciação Mielomonocítica / Antígenos CD / Receptores de Superfície Celular / Placa Aterosclerótica / Macrófagos Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article