Title:Novel Therapeutic Approaches Targeting Matrix Metalloproteinases in Cardiovascular Disease
VOLUME: 12 ISSUE: 10
Author(s):Alexandros Briasoulis, Dimitris Tousoulis, Nikolaos Papageorgiou, Anna-Maria Kampoli, Emmanuel Androulakis, Charalambos Antoniades, Eleftherios Tsiamis, George Latsios and Christodoulos Stefanadis
Affiliation:Department of Medicine; St. Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, USA.
Keywords:Metalloproteinase, tissue inhibitors of metalloproteinases, atherosclerosis, extracellular matrix, degradation, endogenous inhibitors, atherosclerotic plaque, coronary
artery disease, vascular remodelling, heart failure, myocardial infarction, vascular
pathology, pharmacological approaches
to MMP inhibition
Abstract:Matrix metalloproteinases (MMPs), are proteinases that participate in extracellular matrix remodelling and degradation.
Under normal physiological conditions, the activities of MMPs are regulated at the level of transcription, of activation
of the pro-MMP precursor zymogens and of inhibition by endogenous inhibitors (tissue inhibitors of metalloproteinases;
TIMPs). Alteration in the regulation of MMP activity is implicated in atherosclerotic plaque development, coronary
artery disease and heart failure. The pathological effects of MMPs and TIMPs in cardiovascular diseases involve
vascular remodelling, atherosclerotic plaque instability and left ventricular remodelling after myocardial infarction. Since
excessive tissue remodelling and increased matrix metalloproteinase activity have been demonstrated during atherosclerotic
lesion progression, MMPs represent a potential target for therapeutic intervention aimed at modification of vascular
pathology by restoring the physiological balance between MMPs and TIMPs. This review discusses pharmacological approaches
to MMP inhibition.
