title: Angiogenesis and remodelling in human thoracic aortic aneurysms.
abstract: OBJECTIVE
  Human thoracic aneurysm of the ascending aorta (TAA) is a chronic disease characterized by dilatation of the aortic wall, which can progress to vessel dissection and rupture. TAA has several aetiologies, but all forms present common features, including tissue remodelling. Here, we determined and characterized the angiogenic process associated with TAA and its relation with wall remodelling.
  
  
  RESULTS
  Immunostaining for blood vessels showed an increased density of microvessels originating from the adventitia in the external medial layer of TAA compared with healthy aortas. Proteomic array analysis of 55 angiogenic factors in medial and adventitial layers showed different expression profiles in both tissue compartments between aneurysmal and healthy aortas. Quantification by ELISA confirmed that all forms of TAA contained higher levels of several pro- and anti-angiogenic factors, including angiopoietin-1 and -2, fibroblast growth factor-acidic, and thrombospondin-1, than that of healthy aortas. However, all groups showed comparable levels of vascular endothelial growth factor-A. Quantitative RT-PCR demonstrated that angiopoietins were overexpressed in TAA media. Immunostaining and electron microscopy revealed that neovessels had defective endothelial junctions and poor mural cell coverage. This incomplete structure was associated with the accumulation of plasminogen and albumin in the media of TAA.
  
  
  CONCLUSIONS
  We describe, for the first time, leaky neovessel formation in TAA media in association with an imbalance of angiogenic factor levels. Although the initiating mechanisms of neo-angiogenesis in TAA and the potential aetiology-related differences remain to be determined, our results suggest that neo-angiogenesis could participate in TAA wall remodelling and weakening through deposition of blood-borne zymogens.
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, LVTS, UMR-S1148, F-75018 Paris, France INSERM Unit 1148, Hôpital Xavier Bichat, Secteur Claude Bernard, 46 rue Henri Huchard, FR-75877 Paris cedex 18, France ketty.kessler@gmail.com Jean-Baptiste.Michel@inserm.fr.
authors.forename: Ketty
authors.initials: K
authors.lastname: Kessler
authors.affiliation: Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil Department of Morphology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Luciano F
authors.initials: LF
authors.lastname: Borges
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, LVTS, UMR-S1148, F-75018 Paris, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Ho-Tin-Noé
authors.affiliation: Centre National de Référence pour le syndrome de Marfan et apparentés, Hôpital Xavier Bichat, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jondeau
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, LVTS, UMR-S1148, F-75018 Paris, France INSERM Unit 1148, Hôpital Xavier Bichat, Secteur Claude Bernard, 46 rue Henri Huchard, FR-75877 Paris cedex 18, France ketty.kessler@gmail.com Jean-Baptiste.Michel@inserm.fr.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, LVTS, UMR-S1148, F-75018 Paris, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Vranckx
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042501:Angiogenic Proteins / Q000032:analysis / Q000235:genetics; D001013:Aorta, Thoracic / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002199:Capillary Permeability; D016022:Case-Control Studies; D002454:Cell Differentiation; D004108:Dilatation, Pathologic; D005260:Female; D006801:Humans; D008297:Male; D055806:Microvessels / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010641:Phenotype; D040901:Proteomics / Q000379:methods; D066253:Vascular Remodeling; D014661:Vasoconstriction
chemical_list: D042501:Angiogenic Proteins
keywords: Angiogenic balance; Angiopoietins; Marfan; TAA; Thrombospondins