There is growing interest in the role of matrix metalloproteinasesin vascular diseases. These conditions are often characterized by excessive tissue remodelling, and increased matrix metalloproteinase activity has been demonstrated in aneurysms, intimal hyperplasia and atherosclerotic plaque disruption. These enzymes represent a potential target for therapeutic intervention to modify vascular pathology.
The core of this review is derived from a MEDLINE database literature search. The review found that there is convincing evidence of increased matrix metalloproteinase activity in a spectrum of vascular disease. Evidence for an imbalance promoting increased matrix degradation is less well documented. However, studies of matrix metalloproteinase inhibition in vascular disease models suggest potential therapeutic benefit.
In conclusion, in vivo studies of matrix metalloproteinase inhibition are required to further study the potential for reversal or deceleration of the excessive tissue remodelling that accompanies vascular disorders.
Murphy G, Docherty AJP.The matrix metalloproteinases and their inhibitors in connective tissue remodelling. Am J Respir Cell Mol Biol1992; 7: 120-125.
2.
Wysocki AB, Staiano-Coico L, Grinnell F.Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol1993; 101: 64-68.
3.
Page RC.The role of inflammatory mediators in the pathogenesis of periodontal disease. J Periodontal Res1991; 26: 230-242.
4.
Harris E.Rheumatoid arthritis: pathophysiology and implications for therapy. N Engl J Med1990; 322: 1277-1289.
5.
Parsons SL, Watson SA, Brown PD, Collins HM, Steele RJ.Matrix metalloproteinases. Br J Surg1997; 84: 160-166.
6.
Ye S, Humphries S, Henney A.Matrix metalloproteinases: implication in vascular matrix remodelling during atherogenesis. Clin Sci1998; 94: 103-110.
7.
Springman EB, Angleton EL, Birkedal-Hansen H, van Wart HE.Multiple modes of activation of latent human fibroblast collagenase: evidence for the role of a Cys73 active site zinc complex in latency and a cysteine switch mechanism for activation. Proc Natl Acad Sci USA1990; 87: 364-368.
8.
Woessner JF Jr.The family of matrix metalloproteinases. Ann N Y Acad Sci1994; 732: 11-21.
9.
Matrisian LM.Matrix metalloproteinase gene expression. Ann N Y Acad Sci1993; 732: 42-50.
10.
Hibbs M, Hoidal J, Kang A.Expression of a matrix metalloproteinase that degrades native type V collagen and denatured collagens by cultured human alveolar macrophages. J Clin Invest1987; 80: 1644-1650.
11.
Rodgers WH, Osteen KG, Matrisian LM, Navre M, Giudice LC, Gorstein F.Expression and localisation of matrilysin, a matrix metalloproteinase, in human endometrium during the reproductive cycle. Am J Obstet Gynecol1993; 168: 253-260.
12.
Newell KJ, Witty JP, Rodgers WH, Matrisian LM.Expression and localisation of matrix-degrading metalloproteinases during colorectal tumorigenesis. Mol Carcinog1994; 10: 199-206.
13.
Sato H, Takino T, Okada Y, Cao J, Seiki M.A MMP expressed on the cell surface of invasive tumour cells. Nature1994; 370: 61-65.
14.
Gallegos NC, Smales C, Savage FJ, Hembry RM, Boulos PB.The distribution of matrix metalloproteinases and tissue inhibitor of metal-loproteinases in colorectal cancer. Surg Oncol1995; 4: 21-29.
Kirchheimer JC, Remold HG.Functional characteristics of receptor bound urokinase on human monocytes: catalytic efficiency and susceptibility to inactivation by plasminogen activator inhibitors. Blood1989; 74: 1396-1402.
17.
Estreicher A, Wohlwend A, Belin D, Schleuning WD, Vassalli JD.Characterisation of the cellular binding site for the urokinase-typeplasminogen activator. J Biol Chem1989; 264: 1180-1189.
18.
Dollery CM, McEwan JR, Henney AM.Matrix metalloproteinases and cardiovascular disease. Circ Res1995; 77: 863-868.
19.
Ward RV, Hembry RM, Reynolds JJ, Murphy G.The purification of TIMP2 from its 72kDa pro-gelatinase complex. Biochem J1991; 278: 179-187.
20.
Itoh Y, Ito A, Iwata K, Tanzawa K, Mori Y, Nagase H.Plasma membrane-bound tissue inhibitor of metalloproteinases (TIMP)-2 specifically inhibits matrix metalloproteinase 2 (gelatinase A) activated on the cell surface. J Biol Chem1998; 273: 24360-24367.
21.
Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS.Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. J Clin Invest1996; 98: 2572-2579.
22.
Ohara Y, Peterson TE, Harrison DG.Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest1993; 91: 2546-2551.
Woessner JFJ.That impish TIMP: the tissue inhibitor of metalloproteinases-3. J Clin Invest2001; 108: 799-800.
25.
Baker AH, Zaltsman AB, George SJ, Newby AC.Divergent effects of tissue inhibitor of metalloproteinase-1, -2 or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro. J Clin Invest1998; 101: 1478-1487.
26.
Baxter BT, McGee GS, Shively VPet al.Elastin content, cross-links, and mRNA in normal and aneurysmal human aorta. J Vasc Surg1992; 16: 192-200.
27.
He C, Roach M.The composition and mechanical properties of abdominal aortic aneurysms. J Vasc Surg1994; 20: 6-13.
28.
Koch AE, Haines GK, Pearce WH.Human abdominal aortic aneurysms: immunophenotypic analysis suggesting an immune-mediated response. Am J Pathol1990; 137: 1199-1215.
29.
Shah PK.Inflammation, metalloproteinases, and increased proteolysis: an emerging pathophysiological paradigm in aortic aneurysm [Editorial; Comment]. Circulation1997; 96: 2115-2117.
30.
Clark JM, Glagov S.Transmural organisation of the arterial media: the lamellar unit revisited. Arteriosclerosis1985; 5: 19-34.
31.
Dobrin PB, Mrkvicka R.Failure of elastin or collagen as possible critical connective tissue alterations underlying aneurysmal dilatation. Cardiovasc Surg1994; 2: 484-488.
Wills A, Thompson MM, Crowther Met al.Elastase-induced matrix degradation in arterial organ cultures: an in vitro model of aneurysmal disease. J Vasc Surg1996; 24: 667-679.
34.
Anidjar S, Salzmann JL, Gentric D, Lagneau P, Camilleri JP, Michel J-B.Elastase-induced experimental aneurysms in rats. Circulation1990; 82: 973-981.
35.
Anidjar S, Dobrin PB, Eichorst M, Graham GP, Chejfec G.Correlation of inflammatory infiltrate with the enlargement of experimental aortic aneurysms. J Vasc Surg1992; 16: 139-147.
36.
Halpern VJ, Nackman GB, Gandhi RHet al.The elastase infusion model of experimental aortic aneurysms: synchrony of induction of endogenous proteinases with matrix destruction and inflammatory cell response. J Vasc Surg1994; 20: 51-60.
37.
McKusick VA.The defect in Marfan syndrome. Nature1991; 352: 279-281.
38.
Minion DJ, Davis VA, Nejezchleb PA, Wang Y, McManus BM, Baxter BT.Elastin is increased in abdominal aortic aneurysms. J Surg Res1994; 57: 443-446.
White JV, Haas K, Phillips S, Comerota AJ.Adventitial elastolysis is a primary event in aneurysm development. J Vasc Surg1993; 17: 371-380.
41.
Leung D, Glagov S, Mathews M.Cyclical stretching stimulates synthesis of matrix components by arterial smooth muscle cells in vitro. Science1976; 191: 475-477.
42.
McGee GS, Baxter BT, Shively VPet al.Aneurysm or occlusive disease - factors determining the clinical course of atherosclerosis of the infrarenal aorta. Surgery1991; 110: 370-376.
43.
Wills A, Thompson MM, Crowther M, Sayers RD, Bell PF.Pathogenesis of abdominal aortic aneurysms - cellular and biochemical mechanisms. Eur J Vasc Endovasc Surg1996; 12: 391-400.
44.
Busuttil R, Abou-Zamzam AM, Machleder HI.Collagenase activity of the human aorta: a comparison of patients with and without abdominal aortic aneurysms. Arch Surg1980; 115: 1373-1378.
45.
Vine N, Powell JT.Metalloproteinases in degenerative aortic disease. Clin Sci1991; 81: 233-239.
46.
Brophy CM, Sumpio B, Reilly JM, Tilson MD.Electrophoretic characterization of protease expression in aneurysmal aorta: report of a unique 80kDA elastolytic activity. Surg Res Comm1991; 10: 315-321.
47.
Irizarry E, Newman KM, Gandhi RHet al.Demonstration of inter-stitial collagenase in abdominal aortic aneurysm disease. J Surg Res1993; 54: 571-574.
48.
Reilly JM, Brophy CM, Tilson MD.Characterization of an elastase from aneurysmal aorta which degrades intact aortic elastin. Ann Vasc Surg1992; 6: 499-502.
49.
McMillan WD, Patterson BK, Keen RR, Pearce WH.In situ localization and quantification of seventy-two-kilodalton type IV collagenase in aneurysmal, occlusive, and normal aorta. J Vasc Surg1995; 22: 295-305.
50.
Newman KM, Ogata Y, Malon AMet al.Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm. Arterioscler Thromb1994; 14: 1315-1320.
51.
Thompson RW, Holmes DR, Mertens RAet al.Production and localization of 92-kilodalton gelatinase in abdominal aortic aneurysms. An elastolytic metalloproteinase expressed by aneurysm-infiltrating macrophages. J Clin Invest1995; 96: 318-326.
52.
Senior RM, Griffin GL, Fliszar CJ, Shapiro SD, Goldberg GI, Welgus HG.Human 92-kilodalton and 72-kilodalton type IV collagenases are elastases. J Biol Chem1991; 266: 7870-7875.
53.
Tamarina NA, McMillan WD, Shively VP, Pearce WH.Expression of matrix metalloproteinases and their inhibitors in aneurysms and normal aorta. Surgery1997; 122: 264-271.
54.
Knox JB, Sukhova GK, Whittemore AD, Libby P.Evidence for altered balance between matrix metalloproteinases and their inhibitors in human aortic diseases. Circulation1997; 95: 205-212.
55.
Katsuda S, Okada Y, Imai K, Nakanishi I.Matrix metalloproteinases- 9 can degrade arterial elastin. Am J Pathol1994; 145: 1208-1218.
56.
McMillan WD, Patterson BK, Keen RR, Shively VP, Cipollone M, Pearce WH.In situ localisation and quantification of mRNA for 92- kD type IV collagenase and its inhibitor in aneurysmal, occlusive and normal aorta. Arterioscler Thromb Vasc Biol1995; 15: 1139-1144.
57.
Freestone T, Turner RJ, Coady A, Higman DJ, Greenhalgh RM, Powell JT.Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol1995; 15: 1145-1151.
58.
Sakalihasan N, Delvenne P, Nusgens BV, Limet R, Lapiere CM.Activated forms of MMP2 and MMP9 in abdominal aortic aneurysms. J Vasc Surg1996; 24: 127-133.
59.
Patel MI, Melrose J, Ghosh P, Appleberg M.Increased synthesis of matrix metalloproteinases by aortic smooth muscle cells is implicated in the etiopathogenesis of abdominal aortic aneurysms. J Vasc Surg1996; 24: 82-92.
60.
Crowther M, Brindle NJ, Sayers R, Bell PF, Thompson MM.Aneurysmal smooth muscle cells exhibit increased matrix metalloproteinase-2 production in vitro. Ann N Y Acad Sci1996; 800: 283-285.
61.
Carmeliet P, Moons L, Lijnen Ret al.Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation. Nat Genet1997; 17: 439-444.
62.
Davis V, Persidskaia R, Baca-Regen Let al.Matrix metalloproteinase- 2 production and its binding to the matrix are increased in abdominal aortic aneurysms. Arterioscler Throm Vasc Biol1998; 18: 1625-1633.
63.
Loftus IM, McCarthy MJ, Lloyd A, Naylor AR, Bell PF, Thompson MM.Prevalence of true vein graft aneurysms: implications for aneurysm pathogenesis. J Vasc Surg1999; 29: 403-408.
64.
Goodall S, Crowther M, Hemingway D, Bell PRF, Thompson MM.Ubiquitous elevation of MMP-2 expression in the vasculature of patients with abdominal aneurysms. Circulation2001; 104: 304-309.
65.
Thompson RW, Parks WC.Role of matrix metalloproteinases in abdominal aortic aneurysms. Ann N Y Acad Sci1996; 800: 157-174.
66.
Curci JA, Liao S, Huffman MD, Shapiro SD, Thompson RW.Expression and localization of macrophage elastase (matrix metalloproteinase-12) in abdominal aortic aneurysms. J Clin Invest1998; 102: 1900-1910.
67.
Pyo R, Lee JK, Shipley JMet al.Targeted gene disruption of MMP- 9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. J Clin Invest2001; 105: 1641-1649.
68.
Mao D, Lee JK, Van VS, Thompson RW.Expression of collagenase-3 (MMP-13) in human abdominal aortic aneurysms and vascular smooth muscle cells in culture. Biochem Biophys Res Commun1999; 261: 904-910.
Brophy C, Reilly JM, Tilson MD.Decreased tissue inhibitor of metal-loproteinases (TIMP) in abdominal aortic aneurysm tissue: a preliminary report. J Surg Res1991; 50: 653-657.
72.
Tilson MD, Reilly JM, Brophy CM, Webster EL, Barnett TR.Expression and sequence of the gene for tissue inhibitor of metalloproteinases in patients with abdominal aortic aneurysms. J Vasc Surg1993; 18: 266-270.
73.
Allaire E, Forough R, Clowes M, Starcher B, Clowes AW.Local over-expression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model. J Clin Invest1998; 102: 1413-1420.
74.
Wang X, Tromp G, Cole CWet al.Analysis of coding sequences for tissue inhibitor of metalloproteinases 1 (TIMP1) and 2 (TIMP2) in patients with aneurysms. Matrix Biol1999; 18: 121-124.
75.
Todor DR, Lewis I, Bruno G, Chyatte D.Identification of a serum gelatinase associated with the occurrence of cerebral aneurysms as pro-matrix metalloproteinase-2. Stroke1998; 29: 1580-1583.
76.
Peters DG, Kassam A, St-Jean PL, Yonas H, Ferrell RE.Functional polymorphism in the matrix metalloproteinase-9 promoter as a potential risk factor for intracranial aneurysm. Stroke1999; 30: 2612-2617.
77.
McMillan WD, Pearce WH, Thompson RWet al.Increased plasma levels of metalloproteinase-9 are associated with abdominal aortic aneurysms. J Vasc Surg1999; 29: 122-129.
Dilley RJ, McGeachie JK, Prendergast FJ.A review of the histological changes in vein-to-artery grafts, with particular reference to intimal hyperplasia. Arch Surg1988; 123: 691-696.
83.
Sayers R, Jones L, Varty Ket al.The histopathology of infrainguinal vein graft stenoses. Eur J Vasc Surg1993; 7: 16-20.
84.
Mata LA, Bosch X, David PR, Rapold HJ, Corcos T, Bourassa MG.Clinical and angiographic assessment 6 months after double vessel percutaneous angioplasty. J Am Coll Cardiol1985; 6: 1239-1244.
85.
Johnson DE, Hinohara T, Selmon MR, Braden LJ, Simpson JB.Primary peripheral arterial stenoses and restenoses excised by transluminal atherectomy: a histopathological study. J Am Coll Cardiol1990; 15: 419-425.
86.
Schwartz TH, Yates GN, Ghobrial M, Baker WH.Pathologic characteristics of recurrent carotid stenoses. J Vasc Surg1987; 5: 731-737.
87.
Clowes AW, Reidy MA, Clowes MM.Kinetics of cellular proliferation after arterial injury. Lab Invest1983; 49: 327-333.
88.
Ferns GA, Raines EW, Sprugel KH, Motani AS, Reidy MA, Ross R.Inhibition of neointimal smooth muscle cell accumulation after angioplasty by an antibody to PDGF. Science1991; 253: 1129-1132.
89.
Olson NE, Chao S, Lindner V, Reidy MA.Intimal smooth muscle cell proliferation after balloon catheter injury. The role of basic fibroblast growth factor. Am J Pathol1992; 140: 1017-1023.
90.
Johnson JL, van Eys GJJM, Angelini GD, George SJ.Injury induces dedifferentiation of smooth muscle cells and increased matrix-degrading metalloproteinase activity in human saphenous vein. Arterioscler Thromb Vasc Biol2001; 21: 1146-1151.
91.
James TW, Wagner R, White LA, Zwolak RM, Brinkerhoff CE.Induction of collagenase and stromelysin gene expression by mechanical injury in vascular smooth muscle-derived cell line. J Cell Physiol1993; 157: 426-437.
92.
Bendeck MP, Zempo N, Clowes AW, Galardy RE, Reidy MA.Smooth muscle cell migration and matrix metalloproteinase expression after arterial injury in the rat. Circ Res1994; 75: 539-545.
93.
Tyagi SC, Meyer L, Schmaltz RA, Reddy HK, Voelker DJ.Protein-ases and restenosis in the human coronary artery: extracellular matrix production exceeds the expression of proteolytic activity. Atherosclerosis1995; 116: 43-57.
94.
Southgate KM, Fisher M, Banning APet al.Upregulation of basement membrane-degrading metalloproteinase secretion after balloon injury of pig carotid arteries. Circ Res1996; 79: 1177-1187.
95.
Southgate KM, Mehta D, Izzat MB, Newby AC, Angelini GD.Increased secretion of basement membrane-degrading metalloproteinases in pig saphenous vein into carotid artery interposition grafts. Arterioscler Thromb Vasc Biol1999; 19: 1640-1649.
96.
Lijnen HR, Collen SD.Tissue inhibitor of matrix metalloproteinases- 1 impairs arterial neointima formation after vascular injury in mice. Circ Res1999; 85: 1186-1191.
97.
Pauly RR, Passaniti A, Bilato Cet al.Migration of cultured vascular smooth cells through a basement membrane barrier requires type IV collagenase activity and is inhibited by cellular differentiation. Circ Res1994; 75: 41-54.
98.
Mason DP, Kenagy RD, Hasenstab Det al.Matrix metalloproteinase- 9 overexpression enhances vascular smooth muscle cell migration and alters remodelling in the injured rat carotid artery. Circ Res1999; 85: 1179-1185.
99.
Gurjar MV, Sharma RV, Bhalla RC.eNOS gene transfer inhibits smooth muscle cell migration and MMP-2 and MMP-9 activity. Arterioscler Thromb Vasc Biol1999; 19: 2871-2877.
100.
Aoyagi M, Yamamoto M, Azuma Het al.Immunolocalization of matrix metalloproteinases in rabbit carotid arteries after balloon denudation. Histochem Cell Biol1998; 109: 97-102.
101.
Kenagy RD, Hart CE, Stetler-Stevenson WG, Clowes AW.Primate smooth muscle cell migration from aortic explants is mediated by endogenous platelet-derived growth factor and basic fibroblast growth factor acting through matrix metalloproteinases 2 and 9. Circulation1997; 96: 3555-3560.
102.
George SJ, Zaltsman AB, Newby AC.Surgical preparative injury and neointima formation increase MMP-9 expression and MMP-2 activation in human saphenous vein. Cardiovasc Res1997; 33: 447-459.
103.
Porter KE, Thompson MM, Loftus IMet al.Production and inhibition of the gelatinolytic matrix metalloproteinases in a human model of vein graft stenosis. Eur J Vasc Endovasc Surg1999; 17: 404-412.
104.
Porter KE, Loftus IM, Peterson M, Bell RF, London NM, Thompson MM.Marimastat inhibits neointimal thickening in a model of human vein graft stenosis. Br J Surg1998; 85: 1373-1377.
105.
Moons L, Shi C, Ploplis Vet al.Reduced transplant arteriosclerosis in plasminogen-deficient mice. J Clin Invest1998; 102: 1788-1797.
106.
Dollery CM, Humphries SE, McClelland A, Latchman DS, McEwan JR.Expression of tissue inhibitor of matrix metalloproteinases 1 by use of an adenoviral vector inhibits smooth muscle cell migration and reduces neointimal hyperplasia in the rat model of vascular balloon injury. Circulation1999; 99: 3199-3205.
107.
Forough R, Lea H, Starcher Bet al.Metalloproteinase blockade by local overexpression of TIMP-1 increases elastin accumulation in rat carotid artery intima. Arterioscler Thromb Vasc Biol1998; 18: 803-807.
108.
George SJ, Johnson JL, Angelini A, Newby AC, Baker AH.Aden-ovirus-mediated gene transfer of the human TIMP-1 gene inhibits smooth muscle cell migration and neointimal formation in human saphenous vein. Hum Gene Ther1998; 9: 867-877.
109.
Kranzhofer A, Baker AH, George SJ, Newby AC.Expression of tissue inhibitor of metalloproteinase-1, -2, and -3 during neointima formation in organ cultures of human saphenous vein. Arterioscler Thromb Vasc Biol1999; 19: 255-265.
110.
Dollery CM, McEwan JR, Wang M, Sang QA, Liu YE, Shi YE.TIMP-4 is regulated by vascular injury in rats. Circ Res1999; 84: 498-504.
111.
Ross R.The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature1993; 362: 801-809.
112.
Southgate KM, Davies M, Booth RF, Newby AC.Involvement of extracellular-matrix-degrading metalloproteinases in rabbit aortic smooth muscle cell proliferation. Biochem J1992; 288: 93-99.
113.
Falk E, Shah PK, Fuster V.Coronary plaque disruption. Circulation1995: 92: 657-671.
114.
Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT.Macrophage infiltration in acute coronary syndromes. Circulation1994; 90: 775-778.
115.
Buja LM, Willerson JT.Role of inflammation in coronary plaque disruption. Circulation1994; 89: 503-505.
116.
Van der Wal AC, Piek JJet al.Recent activation of the plaque immune response in coronary lesions underlying acute coronary syndromes. Heart1998; 80: 14-18.
117.
Ehara S, Ueda M, Naruko Tet al.Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation2001; 103: 1955-1960.
118.
Elkind MS, Cheng J, Boden-Albala B, Paik MC, Sacco RL.Elevated white blood cell count and carotid plaque thickness: the Northern Manhattan Stroke Study. Stroke2001; 32: 842-849.
119.
Di Napoli M, Papa F, Bocola V.C-reactive protein in ischemic stroke: an independent prognostic factor. Stroke2001; 32: 917-924.
120.
Zwaka TP, Hombach V, Torzewski J.C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation2001; 103: 1194-1197.
121.
Silvestre JS, Mallat Z, Tamarat R, Duriez M, Tedgui A, Levy BI.Regulation of matrix metalloproteinase activity in ischemic tissue by interleukin-10: role in ischemia-induced angiogenesis. Circ Res2001; 89: 259-264.
122.
Smith DA, Irving SD, Sheldon J, Cole D, Kaski JC.Serum levels of the antiinflammatory cytokine interleukin-10 are decreased in patients with unstable angina. Circulation2001; 104: 746-749.
123.
Henney AM, Wakeley PR, Davies MJet al.Localisation of stromelysin gene expression in atherosclerotic plaques by in situ hybridisation. Proc Natl Acad Sci U S A1991; 88: 8154-8158.
124.
Galis ZS, Sukhova GK, Lark MW, Libby P.Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest1994; 94: 2493-2503.
125.
Nikkari ST, O’Brien KD, Ferguson Met al.Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis. Circulation1995; 92: 1393-1398.
126.
Lemaitre V, O’Byrne TK, Borczuk AC, Okada Y, Tall AR, D’Armiento S.ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis. J Clin Invest2001; 107: 1227-1234.
127.
Brown DL, Hibbs MS, Kearney M, Loushin C, Isner JM.Identification of 92-kD gelatinase in human coronary atherosclerotic lesions. Circulation1995; 91: 2125-2131.
128.
Hibbs MS.Expression of 92 kDa phagocyte gelatinase by inflammatory and connective tissue cells. Matrix Suppl1992; 1: 51-57.
129.
Loftus IM, Naylor AR, Goodall Set al.Increased matrix metalloproteinase-9 activity in unstable carotid plaques: a potential role in acute plaque disruption. Stroke2000; 31: 40-47.
130.
Li Z, Li L, Zielke HRet al.Increased expression of 71-kd type IV collagenase (MMP-2) in human aortic atherosclerotic lesions. Am J Pathol1996; 148: 121-128.
131.
Rajavashisth TB, Xu X-P, Jovinge Set al.Membrane type 1 matrix metalloproteinase expression in human atherosclerotic plaques. Circulation1999; 99: 3103-3109.
132.
Halpert I, Sires UI, Roby JDet al.Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localises to areas of versican deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci U S A1996; 93: 9748-9753.
133.
Galis ZS, Sukhova GK, Libby P.Matrix localisation of active pro-teases by in situ zymography: detection of matrix metalloproteinase activity in vascular tissue. FASEB J1995; 9: 974-980.
134.
Zaltsman AB, George SJ, Newby AC.Increased secretion of tissue inhibitors of metalloproteinases 1 and 2 from the aortas of cholesterol fed rabbits partially counterbalances increased metalloproteinase activity. Arterioscler Thromb Vasc Biol1999; 19: 1700-1707.
135.
Rouis M, Adamy C, Duverger Net al.Adenovirus-mediated over-expression of tissue inhibitor of metalloproteinase-1 reduces atherosclerotic lesions in apolipoprotein E-deficient mice. Circulation1999; 100: 533-540.
136.
Aikawa M, Rabkin E, Okada Yet al.Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization. Circulation1998; 97: 2433-2444.
137.
Aikawa M, Rabkin E, Voglic SJet al.Lipid lowering promotes accumulation of mature smooth muscle cells expressing smooth muscle myosin heavy chain isoforms in rabbit atheroma. Circ Res1998; 83: 1015-1026.
138.
Fabunmi RP, Sukhova GK, Sugiyama S, Libby P.Expression of tissue inhibitor of metalloproteinase-3 in human atheroma and regulation in lesion-associated cells. Circ Res1998; 83: 270-278.
139.
Sukhova GK, Schonbeck U, Rabkin Eet al.Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques. Circulation1999; 99: 2503-2509.
140.
Mitchell PG, Magna HA, Reeves LMet al.Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteo-arthritic cartilage. J Clin Invest1996; 97: 761-768.
Kai H, Ikeda H, Yasukawa Het al.Peripheral blood levels of matrix metalloproteases-2 and -9 are elevated in patients with acute coronary syndromes. J Am Coll Cardiol1998; 32: 368-372.
143.
Loftus IM, Naylor AR, Bell PRF, Thompson MM.Plasma MMP-9: a marker of plaque instability. Eur J Vasc Endovasc Surg2001; 21: 17-21.
144.
Montaner J, Alvarez-Sabin J, Molina Cet al.Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment. Stroke2001; 32: 1759-1766.
145.
Rosenberg GA, Sullivan N, Esiri MM.White matter damage is associated with matrix metalloproteinases in vascular dementia. [Editorial comment: matrix metalloproteinases and diffuse white matter injury.] Stroke2001; 32: 1162-1168.
146.
Ye S, Watts GF, Mandalia S, Humphries SE, Henney AM.Preliminary report: genetic variation in the human stromelysin promoter is associated with progression of coronary atherosclerosis. Br Heart J1995; 73: 209-215.
147.
Ye S, Eriksson P, Hamsten A, Kurkinen M, Humphries SE, Henney AM.Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. J Biol Chem1996; 271: 13 055-13 060.
148.
Terashima M, Akita H, Kanazawa Ket al.Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction. Circulation1999; 99: 2717-2719.
149.
Rauramaa R, Vaisanen SB, Luong LAet al.Stromelysin-1 and interleukin-6 gene promoter polymorphisms are determinants of asymptomatic carotid artery atherosclerosis. Arterioscler Thromb Vasc Biol2000; 20: 2657-2662.
150.
Zhang B, Ye S, Herrmann SMet al.Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation1999; 99: 1788-1794.
151.
Alvarez OA, Carmichael DF, DeClerk YA.Inhibition of collagenolytic activity and metastasis of tumour cells by a recombinant human tissue inhibitor of metalloproteinases. J Natl Cancer Inst1990; 82: 589-595.
152.
Hu Y, Baker AH, Zou Y, Newby AC, Xu Q.Local gene transfer of tissue inhibitor of metalloproteinase-2 influences vein graft remodeling in a mouse model. Arterioscler Thromb Vasc Biol2001; 21: 1275-1280.
153.
Schwartz MA, Venkataraman S, Chaffari MA, Libby A, Mookhtiar KA, Mallya SK.Inhibition of human collagenases by sulphur-base substrate analogs. Biochem Biophys Res Commun1991; 176: 173-179.
154.
Watson SA, Morris TM, Parsons SL, Steele RJC, Brown PB.Therapeutic effect of the matrix metalloproteinase inhibitor batimastat in a human colorectal cancer ascites model. Br J Cancer1996; 74: 1354-1358.
Denis LJ, Verweij J.Matrix metalloproteinase inhibitors: present achievements and future prospects. Invest New Drugs1997; 15: 175-185.
157.
Talbot DC, Brown P.Experimental and clinical studies on the use of matrix metalloproteinase inhibitors for the treatment of cancer. Eur J Cancer1996; 32A: 2528-2533.
158.
Bendeck MP, Irvin C, Reidy MA.Inhibition of matrix metalloproteinase activity inhibits smooth muscle cell migration but not neointimal thickening after arterial injury. Circ Res1996; 78: 38-43.
159.
Sierevogel MJ, Pasterkamp G, Velema Eet al.Oral matrix metalloproteinase inhibition and arterial remodeling after balloon dilation: an intravascular ultrasound study in the pig. Circulation2001; 103: 302-307.
160.
Treharne GD, Boyle JR, Goodall S, Loftus IM, Bell PF, Thompson MM.Marimastat inhibits elastin degradation and matrix metalloproteinase 2 activity in a model of aneurysm disease. Br J Surg1999; 86: 1053-1058.
161.
Moore G, Liao S, Curci JAet al.Suppression of experimental abdominal aortic aneurysms by systemic treatment with a hydroxa-mate-based matrix metalloproteinase inhibitor (RS 132908). J Vasc Surg1999; 29: 522-532.
162.
Karwowski JK, Markezich A, Whitson Jet al.Dose-dependent limitation of arterial enlargement by the matrix metalloproteinase inhibitor RS-113,4561. J Surg Res1999; 87: 122-129.
Tamura Y, Watanabe F, Nakatani Tet al.Highly selective and orally active inhibitors of type IV collagenase (MMP-9 and MMP-2): N-sulfonylamino acid derivatives. J Med Chem1998; 41: 640-649.
165.
Greenwald RA, Golub LM, Ramamurthy NS, Chowdhury M, Moak SA, Sorsa T.In vitro sensitivity of the three mammalian collagenases to tetracycline inhibition: relationship to bone and cartilage degradation. Bone1998; 22: 33-38.
166.
Uitto VJ, Firth JD, Nip L, Golub LM.Doxycycline and chemically modified tetracyclines inhibit gelatinase A (MMP-2) gene expression in human skin keratinocytes. Ann N Y Acad Sci1994; 732: 140-151.
167.
Rifkin BR, Vernillo AT, Golub LM.Blocking periodontal disease progression by inhibiting tissue destructive enzymes: a potential therapeutic role for tetracyclines and their chemically-modified analogs. J Periodontol1993; 64: 819-827.
168.
Smith GNJ, Yu LPJ, Brandt KD, Capello WN.Oral administration of doxycycline reduces collagenase and gelatinase activites in extracts of human osteoarthritic cartilage. J Rheumatol1998; 25: 532-535.
169.
Yu LPJ, Smith GNJ, Brandt KD, Myers SL, O’Connor BL, Brandt DA.Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline. Arthritis Rheum1992; 35: 1150-1159.
170.
Shlopov BV, Stuart JM, Gumanovskaya ML, Hasty KA.Regulation of cartilage collagenase by doxycycline. J Rheumatol2001; 28: 835-842.
171.
Cakir Y, Hahn KA.Direct action by doxycycline against canine osteosarcoma cell proliferation and collagenase (MMP-1) activity in vitro. In Vivo1999; 13: 327-331.
172.
Loftus IM, Porter K, Peterson Met al.MMP inhibition reduces intimal hyperplasia in a human vein graft stenosis model. Ann N Y Acad Sci1999; 878: 547-550.
173.
Petrinec D, Liao S, Holmes DR, Reilly JM, Parks WC, Thompson RW.Doxycycline inhibition of aneurysmal degeneration in an elastase-induced rat model of abdominal aortic aneurysm: preservation of aortic elastin associated with suppressed production of 92 kD gelatinase. J Vasc Surg1996; 23: 336-346.
174.
Curci JA, Petrinec D, Liao S, Golub LM, Thompson RW.Pharmacologic suppression of experimental abdominal aortic aneurysms: a comparison of doxycycline and four chemically modified tetracyclines. J Vasc Surg1998; 28: 1082-1093.
175.
Boyle JR, McDermott E, Crowther M, Wills AD, Bell PR, Thompson MM.Doxycycline inhibits elastin degradation and reduces metalloproteinase activity in a model of aneurysmal disease. J Vasc Surg1998; 27: 354-361.
176.
Franklin IJ, Harley SL, Greenhalgh RM, Powell JT.Uptake of tetracycline by aortic aneurysm wall and its effect on inflammation and proteolysis. Br J Surg1999; 86: 771-775.
177.
Thompson RW, Baxter BT.MMP inhibition in abdominal aortic aneurysms: rationale for a prospective randomized clinical trial. Ann N Y Acad Sci1999; 878: 159-178.
178.
Allaire E, Hasenstab D, Kenagy RDet al.Prevention of aneurysm development and rupture by local overexpression of plasminogen activator inhibitor-1. Circulation1998; 98: 249-255.
179.
Franklin IJ, Walton LJ, Greenhalgh RM, Powell JT.The influence of indomethacin on the metabolism and cytokine secretion of human aneurysmal aorta. Eur J Vasc Endovasc Surg1999; 18: 35-42.
180.
Miralles M, Wester W, Sicard GAet al.Indomethacin inhibits expansion of experimental aortic aneurysms via inhibition of the cox2 iso-form of cyclooxygenase. J Vasc Surg1999; 29: 884-893.
181.
Walton LJ, Franklin IJ, Bayston Tet al.Inhibition of prostaglandin E2 synthesis in abdominal aortic aneurysms: implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms. Circulation1999; 100: 48-54.
182.
Barracchini A, Franceschini N, Amicosante Get al.Can non-steroidal anti-inflammatory drugs act as metalloproteinase modulators? An invitro study of inhibition of collagenase activity. J Pharm Pharmacol1998; 50: 1417-1423.
183.
Furberg CD.Natural statins and stroke risk. Circulation1999; 99: 185-188.
184.
Plehn JF, Davis BR, Sacks FMet al.Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) study. Circulation1999; 99: 216-223.
185.
Ballantyne CM, Herd A, Ferlic LLet al.Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy. Circulation1999; 99: 736-743.
186.
Byington RP, Davis BR, Plehn JFet al.Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) project. Circulation2001; 103: 387-392.
187.
Jonsson N, Asplund K.Does pretreatment with statins improve clinical outcome after stroke?: a pilot case-referent study. Stroke2001; 32: 1112-1115.
188.
Corti R, Fayad ZA, Fuster Vet al.Effects of lipid-lowering by simvastatin on human atherosclerotic lesions: a longitudinal study by high-resolution, noninvasive magnetic resonance imaging. Circulation2001; 104: 249-252.
189.
Hughes AD.The role of isoprenoids in vascular smooth muscle: potential benefits of statins unrelated to cholesterol lowering. J Hum Hypertens1996; 10: 387-390.
190.
Corsini A, Raiteri M, Soma MR, Bernini F, Fumagalli R, Paoletti R.Pathogenesis of atherosclerosis and the role of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors. Am J Cardiol1995; 76: 21A-28A.
191.
Corsini A, Pazzucconi F, Arnaboldi Let al.Direct effects of statins on the vascular wall. J Cardiovasc Pharmacol1998; 31: 773-778.
192.
Soma MR, Parolini C, Donetti E, Fumagalli R, Paoletti R.Inhibition of isoprenoid biosynthesis and arterial smooth-muscle cell proliferation. J Cardiovasc Pharmacol1995; 25: S20-S24
193.
Weber C, Erl W, Weber KC, Weber PC.Effects of oxidized low density lipoprotein, lipid mediators and statins on vascular cell interactions. Clin Chem Lab Med1999; 37: 243-251.
194.
Pruefer D, Scalia R, Lefer AM.Simvastatin inhibits leukocyte-endothelial cell interactions and protects against inflammatory processes in normocholesterolemic rats. Arterioscler Thromb Vasc Biol1999; 19: 2894-2900.
195.
Bellosta S, Via D, Canavesi Met al.HMG-CoA reductase inhibitors reduce MMP-9 secretion by macrophages. Arterioscler Thromb Vasc Biol1998; 18: 1671-1678.
196.
Scalia R, Gooszen ME, Jones SPet al.Simvastatin exerts both anti-inflammatory and cardioprotective effects in apolipoprotein E-deficient mice. Circulation2001; 103: 2598-2603.
197.
Aikawa M, Rabkin E, Sugiyama Set al.An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases and tissue factor in vivo and in vitro. Circulation2001; 103: 276-283.
198.
Fukumoto Y, Libby P, Rabkin Eet al.Statins alter smooth muscle cell accumulation and collagen content in established atheroma of watanabe heritable hyperlipidemic rabbits. Circulation2001; 103: 993-999.
199.
Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J.Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation2001; 103: 926-933.
200.
Jialal I, Stein D, Balis D, Grundy SM, Adams-Huet B, Devaraj S.Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation2001; 103: 1933-1935.
201.
Ridker PM, Rifai N, Lowenthal SP.Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation2001; 103: 1191-1193.
