Molecular imaging of matrix metalloproteinases in atherosclerotic plaques

Abstract

<jats:title>Summary</jats:title><jats:p>Ischaemic stroke and myocardial infarction often result from the sudden rupture of an atherosclerotic plaque. The subsequent arterial thrombosis occluding the vessel lumen has been widely indicated as the crucial acute event causing peripheral tissue ischaemia. A complex cross-talk between systemic and intraplaque inflammatory mediators has been shown to regulate maturation, remodeling and final rupture of an atherosclerotic plaque. Matrix metalloproteinases (MMPs) are proteolytic enzymes (released by several cell subsets within atherosclerotic plaques), which favour atherogenesis and increase plaque vulnerability. Thus, the assessment of intraplaque levels and activity of MMP might be of pivotal relevance in the evaluation of the risk of rupture. New imaging approaches, focused on the visualisation of inflammation in the vessel wall and plaque, may emerge as tools for individualised risk assessment and prevention of events. In this review, we summarize experimental findings of the currently available invasive and noninvasive imaging techniques, used to detect the presence and activity of MMPs in atherosclerotic plaques.</jats:p>

Transgenic Overexpression of IL-37 Protects Against Atherosclerosis and Strengthens Plaque Stability

“…The degradation of the extracellular matrix by matrix metalloproteinases (MMPs), which were reported to be secreted by SMCs (SMA high ) and inflammatory cells such as macrophages, T cells and ECs (SMA low ) [29], is thought to contribute to atherosclerotic plaque instability [30]. Therefore, to evaluate whether IL-37 affects atherosclerotic stability, we first measured the collagen content of atherosclerotic plaque sections in mice fed a HFD for 16 weeks.…”

Metalloproteinases promote plaque rupture and myocardial infarction: A persuasive concept waiting for clinical translation

“…Furthermore, selective MMP-12 inhibitors are available and have been used safely in phase II clinical studies in pulmonary disease [58]. Even so, deeply seated MMP-12 positive macrophages might be difficult to inhibit; and therefore a surrogate marker of efficacy, perhaps based on molecular imaging [59], might be needed as a precursor to any outcome trial.…”

“…Such selective targeting appears feasible even with existing chemistries [82]; and innovative approaches are continually emerging [83]. The final missing link is the development of surrogate endpoints, most likely based on non-invasive imaging [59], to bridge the gap between small-scale phase II and costly phase III trials. With continuing energy and enthusiasm all these goals can be achieved.…”

New Targets of Molecular Imaging in Atherosclerosis: Prehension of Current Status

“…Cathepsins and MMPs are highly expressed and localized in rupture-prone areas such as the fibrous cap, plaque shoulder and plaque rupture area. Therefore, cathepsins and MMP as macrophage-related molecules and primary imaging targets have been studied 3,[20][21][22][23][24] (Table 1, Fig. 1).…”

“…13 In addition, 18 F-FDG detects highly increased metabolic activity associated with atherosclerosis since the metabolic activities of cells are increased in the immune response area. 27,28,32 On the other hand, cathepsin protease activity and matrix metalloproteinases activity have been the main targets applied in fluorescent imaging, where diverse imaging probes were developed and used in apoE-/-mice. 2,23 These adhesion molecule and extracellular matrix targets, which are parenchymal components of atherosclerosis, can increase the success of imaging and many studies have in fact shown their application in pre-clinical and clinical trials.…”