Vascular remodeling and protease inhibition--bench to bedside.
Physiological and pathological tissue remodeling needs an orderly degradation of the extracellular matrix. Matrix metalloproteinases (MMPs) are proteases capable of degrading different extracellular matrix components, including collagen and elastin. MMP expression is strongly enhanced in vascular pathologies such as stenosis following balloon dilation, in-stent restenosis, sustained flow changes, aneurysm formation, and atherosclerosis. Experimental studies have revealed that some biological actions of MMPs aggravate a pathological condition, whereas others may be beneficial for the patient suffering from atherosclerotic disease. Therefore, a better understanding of the biological consequence and regulation of MMP activity is critical for the design and potential application of specific MMP inhibitors in vascular disease. In this review, we will give an overview of preclinical experimental studies using MMP inhibitors with the objective to influence vascular occlusive diseases, and we will also highlight new targets that influence MMP expression and activity and that possess potential for therapeutic interventions.
Sluijter
Joost P G
JP
Experimental Cardiology Laboratory, Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Room G02-523, 3584 CX Utrecht, The Netherlands.
de Kleijn
Dominique P V
DP
Pasterkamp
Gerard
G
D000222:Adaptation, Physiological; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D023903:Coronary Restenosis / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases