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Matrix metalloproteinase inhibitor development for the treatment of heart failure
Author(s) -
Peterson J. Thomas,
Li Hua
Publication year - 2002
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10032
Subject(s) - matrix metalloproteinase , heart failure , matrix metalloproteinase inhibitor , medicine , cardiology , pharmacology , drug
Matrix metalloprotease inhibitor (MMPi) drug discovery initially focused on the therapeutic use of these compounds as antineoplastic and antiarthritis agents to reduce metastases and joint matrix degradation, respectively. However, increased MMP expression has been shown to occur after myocardial ischemia (MI) and during progressive heart failure (HF). Inhibition of MMP activity has been shown to limit left ventricular aneurysm, slow atherosclerotic plaque progression, and reduce left ventricular dilation after MI in mice as well as preserving left ventricular geometry and function in several animal HF models. A growing literature indicates that MMPi treatment may represent a novel therapeutic strategy in the treatment for a variety of cardiovascular diseases, especially prevention of heart failure. The objective of this article is to define the role of MMPs in HF, identify which MMPs are upregulated, and outline potential limitations of MMPi therapy in this disease. Drug Dev. Res. 55:29–44, 2002. © 2002 Wiley‐Liss, Inc.