Medical College of Wisconsin
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Matrix metalloproteinases: from biology to therapeutic strategies in cardiovascular disease. J Investig Med 2001 Sep;49(5):381-97

Date

08/29/2001

Pubmed ID

11523694

DOI

10.2310/6650.2001.33783

Scopus ID

2-s2.0-0034888802   41 Citations

Abstract

In this comprehensive review of matrix remodeling, one central theme that bears re-emphasis is the extensivecross-talk and dynamic interactions that exist between terminally differentiated, postmitotic cells, proliferative cells, and the ECM of the cardiovascular system. The activities of MMPs and TIMPs constitute a well-orchestrated contest to maintain tissue integrity and homeostasis. Overexpression of MMPs tilts the balance in favor of irreversible tissue destruction of joints (eg, as in rheumatic disease), and efforts to curtail such errant pathways are ongoing (123). Thrombolytic therapy and percutaneous transluminal coronary angioplasty represent effective strategies for restoring antegrade flow in occluded vessels, but multiple factors preclude most patients with AMI from receiving either of these treatments. Tissue healing and remodeling is a process in which the biology of MMPs becomes universally applicable. Basic lessons from the biochemistry and enzymology of MMPs, combined with the mechanisms of gene expression, will undoubtedly impact the development of future therapies involving MMPs and their endogenous inhibitors. In addition, formidable challenges, ranging from bioavailability to tissue penetration and toxicity in animal models, face investigators using existing pharmacotherapeutics. For congenital diseases, such as Marfan syndrome, which primarily affects the connective tissue, future therapies may be targeted to the underlying pathobiology involving MMPs. Strategies aimed at correction of the genetic defect may be complemented by those to prevent or ameliorate fundamental imbalances in matrix turnover and deposition. The future challenge for cardiovascular medicine is to appropriately shift the pendulum, not to the exclusion of, but to the recognition of the dynamic interaction that exists between myocyte and nonmyocyte populations, which clearly affect the pathogenesis of many acquired and genetic disorders.

Author List

Benjamin IJ

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Arteriosclerosis
Cardiovascular Diseases
Cell Movement
Collagen
Extracellular Matrix
Humans
Marfan Syndrome
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinases
Substrate Specificity
Urokinase-Type Plasminogen Activator
Wound Healing
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