Advertisement

High glucose alters matrix metalloproteinase expression in two key vascular cells: potential impact on atherosclerosis in diabetes

      Abstract

      Diabetes is a major risk factor for atherosclerosis. Hyperglycemia is an underlying contributing factor; however, the mechanisms that mediate the vascular complications are not yet fully understood. In the present study, we provide evidence that elevated glucose induces discordant matrix metalloproteinase (MMP) expression from two key vascular cells, endothelial cells and macrophages. Our results clearly indicate that high glucose (25 mM) induced endothelial cell expression and activity of the collagenase, MMP-1 and the gelatinase, MMP-2, whilst reducing expression of the stromelysin, MMP-3 (P<0.05). Similarly, our results show that high glucose (25 mM) induces expression and activity of MMP-9 from monocyte-derived macrophages (P<0.05). High glucose culture did not affect metalloproteinase inhibitor (TIMP-1) expression. Our results suggest for the first time that high glucose exposure induced discordant regulation of the MMP/TIMP system in vascular cells. The increased MMP-1, MMP-2 and MMP-9 activities induced by high glucose exposure could promote matrix degradation thereby accelerating atherogenesis and potentially reducing plaque stability in diabetes.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ruderman N.
        • Haudenschild C.
        Diabetes as an atherogenic factor.
        Prog. Cardiovasc. Dis. 1984; 26: 373-412
      1. DCCT. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus, New Engl J Med 1993;329:977–86.

        • Fisher E.
        • McLennan S.V.
        • Tada H.
        • Heffernan S.
        • Yue D.K.
        • Turtle J.R.
        Interaction of ascorbic acid and glucose on the production of collagen and proteoglycan by fibroblasts.
        Diabetes. 1991; 40: 371-376
        • Pugliese G.
        • Pricci F.
        • Pugliese F.
        • Mene P.
        • Lenti L.
        • Andreani D.
        • et al.
        Mechanisms of glucose-enhanced extracellular matrix accumulation in rat glomerular mesangial cells.
        Diabetes. 1994; 43: 478-490
        • Gallis Z.
        • Muszynski M.
        • Sukhova G.K.
        • Simon-Morrissey E.
        • Libby P.
        Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions.
        Ann. New York Acad. Sci. 1995; 748: 501-507
        • Shah P.
        • Falk E.
        • Badimon J.J.
        • Fernandez-Ortiz A.
        • Mailhac A.
        • Villareal-Levy G.
        • et al.
        Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques: potential role of matrix-degrading metalloproteinases and implications for plaque rupture.
        Circulation. 1995; 92: 1565-1569
        • Nguyen M.
        • Arkell J.
        • Jackson C.
        Activated protein kinase C directly activates human endothelial gelatinase A.
        J. Biol. Chem. 2000; 275: 9095-9098
        • Winberg J.
        • Kolset S.O.
        • Berg E.
        • Uhlin-Hansen L.
        Macrophages secrete matrix metalloproteinase 9 covalently linked to the core protein of chondroitin sulphate proteoglycans.
        J. Mol. Biol. 2000; 304: 669-680
        • Nagase H.
        • Woessner J.F.
        Matrix metalloproteinases.
        J. Biol. Chem. 1999; 274: 21491-21494
        • Uemura S.
        • Matsushita H.
        • Li W.
        • Glassford A.J.
        • Asagami T.
        • Lee K.-H.
        • et al.
        Diabetes mellitus enhances vascular matix metalloproteinase activity: role of oxidative stress.
        Circ. Res. 2001; 88: 1291-1298
        • McLennan S.V.
        • Fisher E.J.
        • Martell S.Y.
        • Death A.K.
        • Williams P.W.
        • Lyons J.G.
        • et al.
        Effects of glucose on matrix metalloproteinase and plasmin activities in mesangial cells: possible role in diabetic nephropathy.
        Kidney Int. Suppl. 2000; 77: S81-S87
        • McCrohon J.
        • Jessup W.
        • Handelsman D.J.
        • Celermajer D.S.
        Androgen exposure increases human monocyte adhesion to vascular endothelium and endothelial expression of VCAM-1.
        Circulation. 1999; 99: 2317-2322
        • Garner B.
        • Dean R.
        • Jessup W.
        Human macrophage-mediated oxidation of low-density lipoprotein is delayed and independent of superoxide production.
        Biochem. J. 1994; 301: 421-428
        • Death A.K.
        • Yue D.K.
        • Turtle J.R.
        Competitive RT-PCR for measuring metalloproteinase gene expression in human mesangial cells exposed to a hyperglycemic environment.
        BioTechniques. 1999; 27: 512-516
        • McLennan S.V.
        • Fisher E.J.
        • Yue D.K.
        • Turtle J.R.
        High glucose concentration causes a decrease in mesangium degradation. A factor in the pathogenesis of diabetic nephropathy.
        Diabetes. 1994; 43: 1041-1045
        • Goodall S.
        • Crowther M.
        • Hemingway D.M.
        • Bell P.R.
        • Thompson M.M.
        Ubiquitous elevation of matrix metalloproteinase-2 expression in the vasculature of patients with abdominal aneurysms.
        Circulation. 2001; 104: 304-309
        • Thomas C.V.
        • Coker M.L.
        • Zellner J.L.
        • Handy J.R.
        • Crumbley A.J.
        • Spinale F.G.
        Increased matrix metalloproteinase activity and selective upregulation in LV myocardium from patients with end-stage dilated cardiomyopathy.
        Circulation. 1998; 97: 1708-1715
        • Ardans J.A.
        • Blum A.
        • Mangan P.R.
        • Weintroub S.
        • Cannon R.O.
        • Wahl L.M.
        Raloxifene-mediated increase in matrix metalloproteinase-1 production by activated monocytes.
        ATVB. 2001; 21: 1265-1268
        • Lendon C.L.
        • Davies M.J.
        • Born G.V.
        • Richardson P.D.
        Atherosclerotic plaque caps are locally weakened when macrophage density is increased.
        Atherosclerosis. 1991; 87: 87-90
        • Parsons S.L.
        • Watson S.A.
        • Brown P.D.
        • Collins H.M.
        • Steele R.J.
        Matrix metalloproteinases.
        J. Clin. Invest. 1997; 84: 160-166
        • Benbow U.
        • Brinckerhoff C.
        The AP-1 site and MMP gene regulation: what is all the fuss about.
        Matrix Biol. 1997; 15: 519-526
        • Sato H.
        • Kita M.
        • Seiki M.
        v-Src activates the expression of 92-kDa type IV collagenase gene through the AP-1 site and the GT box homologous to retinoblastoma control elements: a mechanism regulating gene expression independent of the by inflammatory cytokines.
        J. Biol. Chem. 1993; 268: 23460-23468
        • Sanz L.
        • Moscat J.
        • Diaz-Meco M.
        Molecular characterization of a novel transcription factor that controls stromelysin expression.
        Mol. Cell. Biol. 1995; 15: 3164-3170
        • Wilmer W.
        • Cosio F.
        DNA binding of activator protein-1 is increased in human mesangial cells cultured in high glucose concentrations.
        Kidney Int. 1998; 53: 1172-1181
        • Du X.
        • Stocklauser-Farber K.
        • Rosen P.
        Generation of reactive oxygen intermediates, activation of NF-kappaB, and induction of apoptosis in human endothelial cells by glucose: role of nitric oxide synthase.
        Free Radic. Biol. Med. 1999; 27: 752-763
        • Okuda Y.
        • Adrogue H.J.
        • Nakajima T.
        • Mizutani M.
        • Asano M.
        • Tachi Y.
        • et al.
        Increased production of PDGF by angiotensin and high glucose in human vascular endothelium.
        Life Sci. 1996; 59: 1455-1461
        • Pascal M.
        • Knott R.
        • Forrester J.
        Glucose mediated regulation of transforming growth factor beta in human retinal endothelial cells.
        Biochem. Soc. Trans. 1996; 24: 228S
        • Kaminska B.
        • Opalka M.
        • Ciereszko R.E.
        • Dusza L.
        Modulation of the composition of AP-1 complex and its impact on transcriptional activity.
        Acta Neurobiol. Exp. 2000; 60: 395-402
        • Abdel Wahab N.
        • Mason R.
        Modulation of neutral protease expression in human mesangial cells by hyperglycemic culture.
        Biochem. J. 1996; 320: 777-783
        • Puyraimond A.
        • Weitzman J.B.
        • Babiole E.
        • Menashi S.
        Examining the relationship between the gelatinolytic balance and the invasive capacity of endothelial cells.
        J. Cell Sci. 1999; 112: 1283-1290