Pro-matrix metalloproteinases (pro-MMP-3) and atherosclerotic carotid artery plaque

This source preferred by Stephen Allen, David Kerr and Ahmed Khattab

Authors: Khattab, A.D., Ali, I.S., Dils, R., Kerr, D., Jenkinson, D.F., Allen, S.C. and Rana, M.

Journal: Biochemical Society Transactions

Volume: 29

Pages: 72

ISSN: 0300-5127

The role of the enzyme MMP-3 in destabilising and disrupting human atherosclerotic carotid plaques has been investigated using immunohistochemical techniques. The level of immunoreactive MMP-3 was higher in echolucent (lipid-laden) than in echogenic (fibrous) plaques, and was mainly concentrated near regions of ulceration and necrosis and areas where fibrous cap was thin or torn. Since the method recognised both active and inactive forms of matrix metalloproteinases (MMPs), it therefore gave no indication of the balance between active enzyme and pro-enzyme.

However, Western blot analysis confirmed that the form of MMP-3 we identified earlier was pro-MMP-3 of molecular weight 57,000KD. Although MMP-9 is the major member of MMPs family involved in plaque destabilisation, its proenzyme is constitutively expressed by monocytes and macrophages, for example in fatty streaks, long before any instability of plaques is observed. The results suggest that the enhanced release of pro- MMP-3 may play a role in the increased extracellular activation of MMP-9. In conclusion, although the classical activation pathway for MMPs in tissues is via plasmin, there is evidence that MMPs can further activate the proenzymes of other MMPs in adjacent tissue. This process might be responsible for subsequent destabilisation and disruption of plaques.

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