title: Topology of protease activities reflects atherothrombotic plaque complexity.
abstract: The pathological remodeling of the arterial wall in atherosclerosis involves protease activities, which play a major role in complications, through plaque rupture. Here, we investigated the release of active proteases by human carotid plaques in relation to (1) the degree of lesion complexity and (2) their compartmentalization between cap, core and media. Eighty human carotid endarterectomy specimens were dissected into culprit stenosing (CPs) and adjacent non-complicated/non-stenosing plaques (NPs). Thirty-five additional CPs were microdissected into cap, core and media. All specimens were compared to control non-atherosclerotic endarteries for the release of components of the plasminogen/plasmin system and matrix metalloproteinases (MMPs). Results show a greater release of the plasminogen activators (PAs), plasmin and active MMPs by CPs compared to NPs, whereas healthy arteries released even lower levels. Furthermore, we highlight a functional interaction between these proteases in human atherosclerotic tissues and more importantly, we demonstrate that the core constitutes the main source of protease activities within CPs. Together, these results suggest that CPs generate plasmin, mainly in the core, which could in turn participate in MMP activation and the onset of complications.
authors.affiliation: INSERM U698, Paris F-75018, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Leclercq
authors.forename: Xavier
authors.initials: X
authors.lastname: Houard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Loyau
authors.forename: Monique
authors.initials: M
authors.lastname: Philippe
authors.forename: Uriel
authors.initials: U
authors.lastname: Sebbag
authors.forename: Olivier
authors.initials: O
authors.lastname: Meilhac
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
mesh_terms: D002339:Carotid Arteries / Q000503:physiopathology*; D002340:Carotid Artery Diseases / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D016893:Carotid Stenosis / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D016894:Endarterectomy, Carotid; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism*
chemical_list: D010447:Peptide Hydrolases; D010960:Plasminogen Activators; D005341:Fibrinolysin; D020782:Matrix Metalloproteinases