Human Vascular Wall Mesenchymal Stromal Cells Contribute to Abdominal Aortic Aneurysm Pathogenesis Through an Impaired Immunomodulatory Activity and Increased Levels of Matrix Metalloproteinase-9

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  • Ciavarella Carmen
    Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna
  • Alviano Francesco
    Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna
  • Gallitto Enrico
    Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna
  • Ricci Francesca
    Immunohaematology and Transfusion Medicine Service, S.Orsola-Malpighi Hospital, University of Bologna
  • Buzzi Marina
    Immunohaematology and Transfusion Medicine Service, S.Orsola-Malpighi Hospital, University of Bologna
  • Velati Claudio
    Immunohaematology and Transfusion Medicine Service, S.Orsola-Malpighi Hospital, University of Bologna
  • Stella Andrea
    Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna
  • Freyrie Antonio
    Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna
  • Pasquinelli Gianandrea
    Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna

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Background:The main histopathological features of abdominal aortic aneurysm (AAA) are tissue proteolysis mediated by matrix metalloproteinases (MMPs) and inflammation. This study aimed at verifying the presence and contribution of mesenchymal stromal cells (MSCs) to aneurysmal tissue remodeling.Methods and Results:MSCs were successfully isolated from the AAA wall of 12 male patients and were found to express mesenchymal and stemness markers. MMP-2/-9 are involved in AAA progression and their mRNA levels in AAA-MSCs resulted higher than healthy MSCs (cMSCs), especially MMP-9 (400-fold increased). Moreover, MMP-9 protein and activity were pronounced in AAA-MSCs. Immunomodulation was tested in AAA-MSCs after co-culture with activated peripheral blood mononuclear cells (PBMCs) and revealed a weak immunosuppressive action on PBMC proliferation (bromodeoxyuridine incorporation, flow cytometry assay), together with a reduced expression of anti-inflammatory molecules (HLA-G, IL-10) by AAA-MSCs compared to cMSCs. MMP-9 expression in AAA-MSCs was shown to be negatively modulated under the influence of cMSCs and exogenous IL-10.Conclusions:MSCs with stemness properties are niched in human AAA tissues and display a dysregulation of functional activities; that is, upregulation of MMP-9 and ineffective immunomodulatory capacity, which are crucial in the AAA progression; the possibility to modulate the increased MMP-9 expression by healthy MSCs and IL-10 suggests that novel therapeutic strategies are possible for slowing down AAA progression. (Circ J 2015; 79: 1460–1469)

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  • Circulation Journal

    Circulation Journal 79 (7), 1460-1469, 2015

    一般社団法人 日本循環器学会

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