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About the Authors:
David H. Lovett
* E-mail: [email protected]
Affiliation: Department of Medicine, San Francisco Department of Veterans Affairs Medical Center, University of California San Francisco, San Francisco, California, United States of America
Rajeev Mahimkar
Current address: BioMarin Pharmaceutical Inc., Novato, California, United States of America
Affiliation: Department of Medicine, San Francisco Department of Veterans Affairs Medical Center, University of California San Francisco, San Francisco, California, United States of America
Robert L. Raffai
Affiliation: Department of Surgery, San Francisco Department of Veterans Affairs Medical Center, University of California San Francisco, San Francisco, California, United States of America
Leslie Cape
Affiliation: Department of Medicine, San Francisco Department of Veterans Affairs Medical Center, University of California San Francisco, San Francisco, California, United States of America
Elena Maklashina
Affiliation: Department of Biochemistry and Biophysics, San Francisco Department of Veterans Affairs Medical Center, University of California San Francisco, San Francisco, California, United States of America
Gary Cecchini
Affiliation: Department of Biochemistry and Biophysics, San Francisco Department of Veterans Affairs Medical Center, University of California San Francisco, San Francisco, California, United States of America
Joel S. Karliner
Affiliations Department of Medicine, San Francisco Department of Veterans Affairs Medical Center, University of California San Francisco, San Francisco, California, United States of America, The Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America
Introduction
Matrix metalloproteinases play a central role in many forms of cardiovascular disease, including valvular disease, ischemia/reperfusion injury, compensatory hypertrophy, post-infarction remodeling and systolic heart failure (Reviewed in [1], [2]). The human matrix metalloproteinase (MMP) gene family is comprised of multiple members with a remarkable diversity of structure, function and regulation. The current nomenclature of this gene family is based on the preferred extracellular matrix molecules cleaved by each enzyme. The gene family has been divided into subgroups consisting of interstitial collagenases (MMP-1,-8,-13), the stromelysins (MMP-3, -10, -11), the matrilysins (MMP-7,-26), the membrane-type MMPs (MT-MMP1-6) and the gelatinases (MMP-2, -9). The proteins share several distinguishing features, included a conserved modular structure, secretion in an inactive zymogen form and dependence on zinc for catalytic activity.
From this diverse group it has become increasingly evident that a specific metalloproteinase, MMP-2, is of central pathophysiologic and therapeutic importance in cardiovascular disease [1], [2]. The primary mRNA...