Matrix metalloproteinases: drug targets for myocardial infarction

Abstract

Myocardial infarction (MI) remains a major cause of morbidity and mortality worldwide. Rapid advances in the treatment of acute MI have significantly improved short-term outcomes in patients, due in large part to successes in preventing myocardial cell death and limiting infarct area during the time of ischemia and subsequent reperfusion. Matrix metalloproteases (MMPs) play key roles in post-MI cardiac remodeling and in the development of adverse outcomes. This review highlights the importance of MMPs in the injury and remodeling response of the left ventricle and also discusses their potential as therapeutic targets Additional pre-clinical and clinical research is needed to further investigate and understand the cardioprotective effects of MMPs inhibitors.

Figure 1

MMP subsites as targets for different classes of MMP inhibitors. Pre – a signal sequence pre-domain, Pro – pro-catalytic domain, Catalytic – catalytic domain, Zn2+ - metal center of the catalytic domain, Hemopexin – hemopexin-like domain (absent in MMP-7 and MMP-26) [142, 143].

Figure 2

Medications used post-MI that directly or indirectly affect MMP production or activity.