Matrix metalloproteinases: a therapeutic target in cardiovascular disease.
Cardiovascular disease is the leading cause of death in Western society. Extracellular matrix turnover is important in many cardiovascular pathologies, such as arterial remodeling, plaque rupture, restenosis, aneurysm formation and heart failure. Matrix metalloproteinases (MMPs) belong to a group of zinc and calcium dependent proteases and cause breakdown of the extracellular matrix. MMP inhibitors have been developed and tested for their effect on the outcome of oncological disease [1]. Recent preclinical research revealed that these MMP inhibitors could also have great potential in the field of cardiovascular disease. This preclinical research has encouraged investigators to design and start the first clinical studies with cardiovascular endpoints. In the present paper, the various aspects of MMP participation in cardiovascular disease will be summarized. Preclinical animal studies that demonstrated the effect and potential of applicable MMP inhibitors on different cardiovascular disease entities will be discussed. We will specifically focus on the role of MMPs and the potential of their inhibitors in de novo atherosclerotic plaque destabilization, arterial remodeling, restenosis after ballon angioplasty and stenting, aneurysm formation and heart failure. We conclude that MMP inhibitors are likely to be useful in the development of pharmacological approaches to reduce cardiovascular death, considering the positive outcomes after usage of MMP inhibitors in restenosis and arterial remodeling.
Sierevogel
M J
MJ
Department of Cardiology, University Medical Center, Utrecht, The Netherlands. g.pasterkamp@hli.azu.nl
Pasterkamp
G
G
de Kleijn
D P V
DP
Strauss
B H
BH
D000783:Aneurysm / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001161:Arteriosclerosis / Q000188:drug therapy / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D019714:Tissue Inhibitor of Metalloproteinases / Q000627:therapeutic use*
D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases