title: Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme.
abstract: Certain matrix metalloproteinases (MMP) are expressed within the fibrous areas surrounding acellular lipid cores of atherosclerotic plaques, suggesting that these proteinases degrade matrix proteins within these areas and weaken the structural integrity of the lesion. We report that matrilysin and macrophage metalloelastase, two broad-acting MMPs, were expressed in human atherosclerotic lesions in carotid endarterectomy samples (n = 18) but were not expressed in normal arteries (n = 7). In situ hybridization and immunohistochemistry revealed prominent expression of matrilysin in cells confined to the border between acellular lipid cores and overlying fibrous areas, a distribution distinct from other MMPs found in similar lesions. Metalloelastase was expressed in these same border areas. Matrilysin was present in lipid-laden macrophages, identified by staining with anti-CD-68 antibody. Furthermore, endarterectomy tissue in organ culture released matrilysin. Staining for versican demonstrated that this vascular proteoglycan was present at sites of matrilysin expression. Biochemical studies showed that matrilysin degraded versican much more efficiently than other MMPs present in atherosclerotic lesions. Our findings suggest that matrilysin, specifically expressed in atherosclerotic lesions, could cleave structural proteoglycans and other matrix components, potentially leading to separation of caps and shoulders from lipid cores.
authors.affiliation: Division of Cardiology, Barnes-Jewish Hospital, St. Louis, MO 63110, USA.
authors.forename: I
authors.initials: I
authors.lastname: Halpert
authors.forename: U I
authors.initials: UI
authors.lastname: Sires
authors.forename: J D
authors.initials: JD
authors.lastname: Roby
authors.forename: S
authors.initials: S
authors.lastname: Potter-Perigo
authors.forename: T N
authors.initials: TN
authors.lastname: Wight
authors.forename: S D
authors.initials: SD
authors.lastname: Shapiro
authors.forename: H G
authors.initials: HG
authors.lastname: Welgus
authors.forename: S A
authors.initials: SA
authors.lastname: Wickline
authors.forename: W C
authors.initials: WC
authors.lastname: Parks
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001161:Arteriosclerosis / Q000201:enzymology* / Q000473:pathology; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D017403:In Situ Hybridization; D037181:Lectins, C-Type; D008264:Macrophages / Q000201:enzymology*; D053508:Matrix Metalloproteinase 12; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000378:metabolism; D009924:Organ Culture Techniques; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases; D053675:Versicans; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D011508:Chondroitin Sulfate Proteoglycans; D006023:Glycoproteins; D037181:Lectins, C-Type; D053508:Matrix Metalloproteinase 12; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D053675:Versicans; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C508322:VCAN protein, human; C507122:MMP12 protein, human