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Review

Therapeutic potential of matrix metalloproteinase inhibitors in atherosclerosis

Pages 993-1007 | Published online: 24 Feb 2005

Bibliography

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  • •It is suggested in this paper that oxidised LDL stimulates MMP-9 in macrophages, whilst reducing TIMP-1 expression.
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  • ••This work clearly shows that CD40 ligation is involved inatherosclerotic plaque formation in mice lacking the LDL receptor.
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  • •The authors of this work suggest that MMP inhibitors may not be suitable for the treatment of atherosclerosis since treatment with a MMP inhibitor did not reduce lesion size or intimal thickening in rats.
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  • •Demonstrated that increasing production of TIMP-1 by gene transfer in injured rat vessels reduces intimal thickening and suggests that this type of strategy may be useful in the treatment of atherosclerosis.
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  • •See reference 113 for annotation.
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  • •See reference 113 for annotation.
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  • •Using human saphenous veins, this paper further supports the potential use of gene therapy using TIMPs, which may be useful for the treatment of atherosclerosis.
  • GEORGE SJ, JOHNSON JL, ANGELINI GD, NEWBY AC, BAKER AH: Adenovirus-mediated gene transfer of the human TIMP-1 gene inhibits SMC migration and neointima formation in human saphenous vein. Hum. Gene Ther. (1998) 9:867–877.
  • •See reference 116 for annotation.
  • CHENG L, MANTILE G, PAULY R et al.: Adenovirus-mediated gene transfer of the human tissue inhibitor of metalloproteinase-2 blocks vascular smooth muscle cell invasiveness in vitro and modulates neointimal development in vivo. Circulation (1998) 98(20)2195–2201.
  • GEORGE SJ, LLOYD CT, ANGELINI GD, NEWBY AC, BAKER AH: Inhibition of late vein graft neointima formation in human and porcine modles by adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-3. Circulation (2000) 101:296–304.
  • •This study suggests that TIMP-3 may be the best candidate for gene therapy treatment with TIMPs since it not only inhibits the activity of MMPs but also stimulates apoptosis.
  • ROUIS M, ADAMY C, DUVERGER N et al.: Adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-1 reduces atherosclerotic lesions in apolipoprotein E-deficient mice. Circulation (1999) 100(5)533–540.
  • ••This interesting study is the most direct demonstration todate, that gene therapy using TIMPs may be useful in the treatment of atheroscelerosis.
  • BECKETT RP, DAVIDSON AH, DRUMMOND AH, HUXLEY P, WHITTAKER M: Recent advances in matrix metallo-proteinase inhibitor. Drug Dis. Today (1996) 1:16–26.
  • SANTOS 0, MCDERMOTT CD, DANIELS RG, APPELT K: Rodent pharmokinetic and anti-tumour efficacy studies with a series of synthetic inhibitors if matrix metalloproteinases. Clin. Exp. Metast. (1997) 15:499–508.
  • WOJTOWICZ-PRAGA S, TORRI J, JOHNSON M et al.: Phase I trial of Marmistat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer. J. Clin. Oncol. (1998) 16:2150–2156.
  • KOIVUNEN E, ARAP W, VALTANEN H et al.: Tumor targeting with a selective gelatinase inhibitor. Nature Biotech. (1999) 17:768–774.
  • ••This novel study highlights the potential of this type ofstrategy for inhibiting MMP activity.

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