title: Tissue diffusion and retention of metalloproteinases in ascending aortic aneurysms and dissections.
abstract: Histopathological alterations in human aneurysms and dissections of the thoracic ascending aorta include areas of mucoid degeneration within the medial layer, colocalized with areas of cell disappearance and disruption of extracellular matrix elastic and collagen fibers. We studied the presence of matrix metalloproteinases in relation to their capacity to diffuse through the tissue or to be retained in areas of mucoid degeneration in aneurysms and dissections of the ascending aorta. Ascending aortas from 9 controls, 33 patients with aneurysms, and 14 with acute dissections, all collected at surgery, were analyzed. The morphological aspect was similar whatever the etiology or phenotypic expression of the pathological aortas, involving areas of extracellular matrix breakdown and cell rarefaction associated with mucoid degeneration. Release of proMMP-2, constitutively expressed by smooth muscle cells, was not different between controls and aneurysmal aortas, whereas the aneurysmal aortas released more of the active form. Release of pro and active MMP-9 was also similar between controls and aneurysmal aortas. Immunohistochemical staining of MMP-2 and MMP-9 was weak in both control and pathological aortas. In contrast, released MMP-7 (matrilysin) and MMP-3 (stromelysin-1) could not be detected in conditioned media but were present in tissue extracts with no detectable quantitative difference between controls and pathological aortas. Immunohistochemical staining of MMP-7 and MMP-3 revealed their retention in areas of mucoid degeneration, and semiquantitative evaluation of immunostaining showed more MMP-7 in pathological aortas than in controls. In conclusion, areas of mucoid degeneration, the hallmark of aneurysms, and dissections of thoracic ascending aortas, whatever their etiology, are not inert and can retain specific proteases.
authors.affiliation: Inserm, Unit 698, Cardiovascular Hemostasis, Bio-Engineering and Remodeling, CHU Hôpital Bichat, 75018 Paris, France.
authors.forename: Luciano F
authors.initials: LF
authors.lastname: Borges
authors.forename: Ziad
authors.initials: Z
authors.lastname: Touat
authors.forename: Anne
authors.initials: A
authors.lastname: Leclercq
authors.forename: Ayman Al Haj
authors.initials: AA
authors.lastname: Zen
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jondeau'
authors.forename: Brigitte
authors.initials: B
authors.lastname: Franc
authors.forename: Monique
authors.initials: M
authors.lastname: Philippe
authors.forename: Olivier
authors.initials: O
authors.lastname: Meilhac
authors.forename: Paulo S
authors.initials: PS
authors.lastname: Gutierrez
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
mesh_terms: D000784:Aortic Dissection / Q000201:enzymology* / Q000473:pathology; D001013:Aorta, Thoracic / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D001014:Aortic Aneurysm / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007124:Immunoenzyme Techniques; D045726:Metalloproteases / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism; D017540:Tunica Media / Q000201:enzymology / Q000473:pathology
chemical_list: D017077:Culture Media, Conditioned; D009077:Mucins; D045726:Metalloproteases