title: Human Vascular Wall Mesenchymal Stromal Cells Contribute to Abdominal Aortic Aneurysm Pathogenesis Through an Impaired Immunomodulatory Activity and Increased Levels of Matrix Metalloproteinase-9.
abstract: 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.
  
  
  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.
authors: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna.
authors: Carmen
authors: C
authors: Ciavarella
authors: Francesco
authors: F
authors: Alviano
authors: Enrico
authors: E
authors: Gallitto
authors: Francesca
authors: F
authors: Ricci
authors: Marina
authors: M
authors: Buzzi
authors: Claudio
authors: C
authors: Velati
authors: Andrea
authors: A
authors: Stella
authors: Antonio
authors: A
authors: Freyrie
authors: Gianandrea
authors: G
authors: Pasquinelli
mesh_terms: D000368:Aged; D001012:Aorta, Abdominal / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D018920:Coculture Techniques; D018450:Disease Progression; D059951:HLA-G Antigens / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D008875:Middle Aged; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D059951:HLA-G Antigens; C508609:IL10 protein, human; D007155:Immunologic Factors; D012333:RNA, Messenger; D016753:Interleukin-10; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9