Matrix Metalloproteinases in Vascular Disease - A Potential Therapeutic Target?
Chung S. Lim, Joseph Shalhoub, Manjit S. Gohel, Amanda C. Shepherd and Alun H. Davies
Pages 75-85 (11)
Introduction: This paper aims to summarize the scientific rationale and future perspectives in the development of effective matrix metalloproteinase (MMP) modulators in the management of patients with arterial and venous disease. Methods: Pubmed, Embase and Cinahl databases were searched using the search terms ‘MMP’, ’matrix metalloproteinase’, ‘arterial disease’, ‘venous disease’, ‘aneurysm’, ‘vascular disease’, ‘atherosclerosis’ and ‘varicose veins’. Articles focussing on aneurysm disease, peripheral arterial disease, carotid stenosis and venous disorders were included. Results: Animal studies assessing MMP expression have demonstrated that MMP-2 and MMP-9 may contribute to arterial aneurysm formation and in atherosclerosis. Human studies and animal models have shown that MMP-3 and MMP-9 may have a protective role against plaque development and destabilization whereas MMP-12 might promote these changes. In venous disease, increased expression of MMP-1, MMP-9 and MMP-13 have been shown in human varicose veins. MMP- 2 and MMP-9 were also shown to be upregulated in experimentally induced venous hypertension and higher concentrations of MMP-2 in wound exudate and biopsies have been shown to correlate with impaired venous ulcer healing. The use of statins has become widespread in patients with arterial disease and MMP inhibition is likely to contribute to the mechanism of action. More selective MMP modulators are currently being developed, although clinical studies are currently lacking. Conclusions: MMPs have been directly implicated in the pathophysiology of many arterial and venous disorders and remain an important potential therapeutic target. Studies are needed to further develop and demonstrate the clinical benefits of MMP modulating agents.
Matrix metalloproteinases, arterial disease, venous disease, atherosclerosis, aneurysm, chronic venous disease
Imperial Vascular Unit, 4 North, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, UK.