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Vascular Biology

Role of Proinflammatory CD68+MR− Macrophages in Peroxiredoxin-1 Expression and in Abdominal Aortic Aneurysms in Humans

Ludovic Boytard, Rafaelle Spear, Giulia Chinetti-Gbaguidi, Adelina E. Acosta-Martin, Jonathan Vanhoutte, Nicolas Lamblin, Bart Staels, Philippe Amouyel, Stephan Haulon, Florence Pinet
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https://doi.org/10.1161/ATVBAHA.112.300663
Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;ATVBAHA.112.300663
Originally published December 13, 2012
Ludovic Boytard
From the INSERM, U744 (L.B., R.S., A.E.A.-M., N.L., P.A., F.P.), INSERM, U1011 (G.C.-G., J.V.), and INSERM, U1008 (S.H.), Lille, France; Institut Pasteur de Lille, Lille, France (L.B., R.S., G.C.-G., A.E.A.-M., J.V., N.L., B.S., P.A., F.P.); Univ Lille Nord de France, IFR142, Lille, France (L.B., R.S., A.E.A.-M., N.L., B.S., P.A., F.P.); Centre Hospitalier Régional et Universitaire de Lille, Lille, France (R.S., N.L., P.A., S.H., F.P.); and Univ Lille Nord de France, IFR114, Lille, France (G.C.-G., J.V., B.S., S.H.).
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Rafaelle Spear
From the INSERM, U744 (L.B., R.S., A.E.A.-M., N.L., P.A., F.P.), INSERM, U1011 (G.C.-G., J.V.), and INSERM, U1008 (S.H.), Lille, France; Institut Pasteur de Lille, Lille, France (L.B., R.S., G.C.-G., A.E.A.-M., J.V., N.L., B.S., P.A., F.P.); Univ Lille Nord de France, IFR142, Lille, France (L.B., R.S., A.E.A.-M., N.L., B.S., P.A., F.P.); Centre Hospitalier Régional et Universitaire de Lille, Lille, France (R.S., N.L., P.A., S.H., F.P.); and Univ Lille Nord de France, IFR114, Lille, France (G.C.-G., J.V., B.S., S.H.).
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Giulia Chinetti-Gbaguidi
From the INSERM, U744 (L.B., R.S., A.E.A.-M., N.L., P.A., F.P.), INSERM, U1011 (G.C.-G., J.V.), and INSERM, U1008 (S.H.), Lille, France; Institut Pasteur de Lille, Lille, France (L.B., R.S., G.C.-G., A.E.A.-M., J.V., N.L., B.S., P.A., F.P.); Univ Lille Nord de France, IFR142, Lille, France (L.B., R.S., A.E.A.-M., N.L., B.S., P.A., F.P.); Centre Hospitalier Régional et Universitaire de Lille, Lille, France (R.S., N.L., P.A., S.H., F.P.); and Univ Lille Nord de France, IFR114, Lille, France (G.C.-G., J.V., B.S., S.H.).
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Adelina E. Acosta-Martin
From the INSERM, U744 (L.B., R.S., A.E.A.-M., N.L., P.A., F.P.), INSERM, U1011 (G.C.-G., J.V.), and INSERM, U1008 (S.H.), Lille, France; Institut Pasteur de Lille, Lille, France (L.B., R.S., G.C.-G., A.E.A.-M., J.V., N.L., B.S., P.A., F.P.); Univ Lille Nord de France, IFR142, Lille, France (L.B., R.S., A.E.A.-M., N.L., B.S., P.A., F.P.); Centre Hospitalier Régional et Universitaire de Lille, Lille, France (R.S., N.L., P.A., S.H., F.P.); and Univ Lille Nord de France, IFR114, Lille, France (G.C.-G., J.V., B.S., S.H.).
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Jonathan Vanhoutte
From the INSERM, U744 (L.B., R.S., A.E.A.-M., N.L., P.A., F.P.), INSERM, U1011 (G.C.-G., J.V.), and INSERM, U1008 (S.H.), Lille, France; Institut Pasteur de Lille, Lille, France (L.B., R.S., G.C.-G., A.E.A.-M., J.V., N.L., B.S., P.A., F.P.); Univ Lille Nord de France, IFR142, Lille, France (L.B., R.S., A.E.A.-M., N.L., B.S., P.A., F.P.); Centre Hospitalier Régional et Universitaire de Lille, Lille, France (R.S., N.L., P.A., S.H., F.P.); and Univ Lille Nord de France, IFR114, Lille, France (G.C.-G., J.V., B.S., S.H.).
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Nicolas Lamblin
From the INSERM, U744 (L.B., R.S., A.E.A.-M., N.L., P.A., F.P.), INSERM, U1011 (G.C.-G., J.V.), and INSERM, U1008 (S.H.), Lille, France; Institut Pasteur de Lille, Lille, France (L.B., R.S., G.C.-G., A.E.A.-M., J.V., N.L., B.S., P.A., F.P.); Univ Lille Nord de France, IFR142, Lille, France (L.B., R.S., A.E.A.-M., N.L., B.S., P.A., F.P.); Centre Hospitalier Régional et Universitaire de Lille, Lille, France (R.S., N.L., P.A., S.H., F.P.); and Univ Lille Nord de France, IFR114, Lille, France (G.C.-G., J.V., B.S., S.H.).
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Bart Staels
From the INSERM, U744 (L.B., R.S., A.E.A.-M., N.L., P.A., F.P.), INSERM, U1011 (G.C.-G., J.V.), and INSERM, U1008 (S.H.), Lille, France; Institut Pasteur de Lille, Lille, France (L.B., R.S., G.C.-G., A.E.A.-M., J.V., N.L., B.S., P.A., F.P.); Univ Lille Nord de France, IFR142, Lille, France (L.B., R.S., A.E.A.-M., N.L., B.S., P.A., F.P.); Centre Hospitalier Régional et Universitaire de Lille, Lille, France (R.S., N.L., P.A., S.H., F.P.); and Univ Lille Nord de France, IFR114, Lille, France (G.C.-G., J.V., B.S., S.H.).
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Philippe Amouyel
From the INSERM, U744 (L.B., R.S., A.E.A.-M., N.L., P.A., F.P.), INSERM, U1011 (G.C.-G., J.V.), and INSERM, U1008 (S.H.), Lille, France; Institut Pasteur de Lille, Lille, France (L.B., R.S., G.C.-G., A.E.A.-M., J.V., N.L., B.S., P.A., F.P.); Univ Lille Nord de France, IFR142, Lille, France (L.B., R.S., A.E.A.-M., N.L., B.S., P.A., F.P.); Centre Hospitalier Régional et Universitaire de Lille, Lille, France (R.S., N.L., P.A., S.H., F.P.); and Univ Lille Nord de France, IFR114, Lille, France (G.C.-G., J.V., B.S., S.H.).
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Stephan Haulon
From the INSERM, U744 (L.B., R.S., A.E.A.-M., N.L., P.A., F.P.), INSERM, U1011 (G.C.-G., J.V.), and INSERM, U1008 (S.H.), Lille, France; Institut Pasteur de Lille, Lille, France (L.B., R.S., G.C.-G., A.E.A.-M., J.V., N.L., B.S., P.A., F.P.); Univ Lille Nord de France, IFR142, Lille, France (L.B., R.S., A.E.A.-M., N.L., B.S., P.A., F.P.); Centre Hospitalier Régional et Universitaire de Lille, Lille, France (R.S., N.L., P.A., S.H., F.P.); and Univ Lille Nord de France, IFR114, Lille, France (G.C.-G., J.V., B.S., S.H.).
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Florence Pinet
From the INSERM, U744 (L.B., R.S., A.E.A.-M., N.L., P.A., F.P.), INSERM, U1011 (G.C.-G., J.V.), and INSERM, U1008 (S.H.), Lille, France; Institut Pasteur de Lille, Lille, France (L.B., R.S., G.C.-G., A.E.A.-M., J.V., N.L., B.S., P.A., F.P.); Univ Lille Nord de France, IFR142, Lille, France (L.B., R.S., A.E.A.-M., N.L., B.S., P.A., F.P.); Centre Hospitalier Régional et Universitaire de Lille, Lille, France (R.S., N.L., P.A., S.H., F.P.); and Univ Lille Nord de France, IFR114, Lille, France (G.C.-G., J.V., B.S., S.H.).
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Abstract

Objective—Abdominal aortic aneurysms (AAAs), dilations of the infrarenal aorta, are characterized by inflammation and oxidative stress. We previously showed increased levels of peroxiredoxin-1 (PRDX-1) in macrophages cultured from AAA patients. The purpose of the study was to determine which subpopulation of macrophages is present in AAAs and is involved in upregulation of PRDX-1 in aneurysmal disease.

Methods and Results—This study used immunohistochemistry with antibodies against CD68 and mannose receptor (MR) to determine the subtype of macrophages in AAA tissue samples (n=33); laser capture microdissection to isolate each subtype; and quantitative–reverse transcriptase-polymerase chain reaction, Western blot, and ELISA to assess PRDX-1 mRNA and PRDX-1protein levels in both types. Proinflammatory CD68+MR− macrophages predominated in adventitial tissue, whereas the intraluminal thrombus contained CD68+MR+ macrophages. The presence of lipids and iron-containing deposits confirmed their phagocytic phenotype. Laser capture microdissection-isolated CD68+MR− and CD68+MR+ macrophages, characterized by quantitative–reverse transcriptase-polymerase chain reaction (TNF, IL1B, MRC1, and CCL18) and Western blot (stabilin and hemoglobin), validated the microdissected subtypes. PRDX-1 expression was colocalized with CD68+MR− macrophages. PRDX-1 mRNA and PRDX-1 protein were both more abundant in CD68+MR− than CD68+MR+ macrophages in AAA.

Conclusion—These findings suggest that the proteins or mRNAs expressed by the proinflammatory CD68+MR− macrophages may contribute to aneurysmal pathology.

  • abdominal aortic aneurysm
  • human
  • immunohistochemistry
  • laser capture microdissection
  • macrophages
  • Received August 8, 2012.
  • Accepted November 29, 2012.
  • © 2012 American Heart Association, Inc.
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    Role of Proinflammatory CD68+MR− Macrophages in Peroxiredoxin-1 Expression and in Abdominal Aortic Aneurysms in Humans
    Ludovic Boytard, Rafaelle Spear, Giulia Chinetti-Gbaguidi, Adelina E. Acosta-Martin, Jonathan Vanhoutte, Nicolas Lamblin, Bart Staels, Philippe Amouyel, Stephan Haulon and Florence Pinet
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;ATVBAHA.112.300663, originally published December 13, 2012
    https://doi.org/10.1161/ATVBAHA.112.300663

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    Role of Proinflammatory CD68+MR− Macrophages in Peroxiredoxin-1 Expression and in Abdominal Aortic Aneurysms in Humans
    Ludovic Boytard, Rafaelle Spear, Giulia Chinetti-Gbaguidi, Adelina E. Acosta-Martin, Jonathan Vanhoutte, Nicolas Lamblin, Bart Staels, Philippe Amouyel, Stephan Haulon and Florence Pinet
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;ATVBAHA.112.300663, originally published December 13, 2012
    https://doi.org/10.1161/ATVBAHA.112.300663
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