title: Myocardial matrix metalloproteinase-2: inside out and upside down.
abstract: Since their inaugural discovery in the early 1960s, matrix metalloproteinases (MMPs) have been shown to mediate multiple physiological and pathological processes. In addition to their canonical function in extracellular matrix (ECM) remodeling, research in the last decade has highlighted new MMP functions, including proteolysis of novel substrates beyond ECM proteins, MMP localization to subcellular organelles, and proteolysis of susceptible intracellular proteins in those subcellular compartments. This review will provide a comparison of the extracellular and intracellular roles of MMPs, illustrating that MMPs are far more interesting than the one-dimensional view originally taken. We focus on the roles of MMP-2 in cardiac injury and repair, as this is one of the most studied MMPs in the cardiovascular field. We will highlight how understanding all dimensions, such as localization of activity and timing of interventions, will increase the translational potential of research findings. Building upon old ideas and turning them inside out and upside down will help us to better understand how to move the MMP field forward.
authors.affiliation: San Antonio Cardiovascular Proteomics Center; Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: DeCoux
authors.affiliation: San Antonio Cardiovascular Proteomics Center; Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA; Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS, USA.
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
authors.affiliation: University of California, San Diego, School of Medicine, Cardiology Division, San Diego, CA, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Villarreal
authors.affiliation: University of California, San Diego, School of Medicine, Cardiology Division, San Diego, CA, USA; Bristol-Myers Squibb Company, Pennington, NJ, USA.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Garcia
authors.affiliation: Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, Departments of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta Canada. Electronic address: richard.schulz@ualberta.ca.
authors.forename: Richard
authors.initials: R
authors.lastname: Schulz
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000201:enzymology*; D005109:Extracellular Matrix / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress; D021381:Protein Transport; D059748:Proteolysis
chemical_list: D007527:Isoenzymes; D061965:Matrix Metalloproteinase Inhibitors; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Cardiovascular disease; Doxycycline; Heart failure; MMP-2; Myocardial ischemia and infarction; TIPTOP