Matrix metalloproteinases: Influence on smooth muscle cells and atherosclerotic plaque stability

Jason Lee Johnson*

*Corresponding author for this work

    Research output: Contribution to journalReview article (Academic Journal)peer-review

    138 Citations (Scopus)


    Atherosclerotic plaque rupture, with subsequent occlusive thrombosis, is the underlying cause of most cases of sudden cardiac death. Matrix metalloproteinases (MMPs) are thought to mediate the progression of stable atherosclerotic lesions to an unstable phenotype that is prone to rupture through the destruction of strength-giving extracellular matrix (ECM) proteins. Smooth muscle cells secrete and deposit ECM proteins and are, therefore, considered protective against atherosclerotic plaque destabilization. However, similar to inflammatory cells (e.g., macrophages), smooth muscle cells release numerous MMPs that are capable of digesting ECM proteins. Thus, the interaction of smooth muscle cells and MMPs in atherosclerotic plaques is complex and not fully understood. Recently, research into the roles of MMPs and their endogenous inhibitors (tissue inhibitors of metalloproteinases), and their effects on smooth muscle behavior during plaque destabilization has been aided by the development of reproducible animal models of plaque instability. A plethora of studies has demonstrated that MMPs directly modulate smooth muscle behavior with both beneficial and deleterious effects on atherosclerotic plaque stability, in addition to their canonical effects on ECM remodeling. Consequently, broad-spectrum MMP inhibition may inhibit plaque-stabilizing mechanisms, such as smooth muscle cell growth, while conversely retarding ECM destruction and subsequent rupture. Hence the development of selective MMP inhibitors, that spare inhibitory effects on smooth muscle cell function, may be useful therapies to prevent plaque rupture and in this regard MMP-12 appears to be a particularly attractive target.

    Original languageEnglish
    Pages (from-to)265-282
    Number of pages18
    JournalExpert Review of Cardiovascular Therapy
    Issue number2
    Publication statusPublished - 1 Mar 2007


    • Apoptosis
    • Atherosclerosis
    • Matrix metalloproteinases
    • Migration
    • Plaque rupture
    • Proliferation
    • Smooth muscle cells


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