title: The impact of aging on cardiac extracellular matrix.
abstract: Age-related changes in cardiac homeostasis can be observed at the cellular, extracellular, and tissue levels. Progressive cardiomyocyte hypertrophy, inflammation, and the gradual development of cardiac fibrosis are hallmarks of cardiac aging. In the absence of a secondary insult such as hypertension, these changes are subtle and result in slight to moderate impaired myocardial function, particularly diastolic function. While collagen deposition and cross-linking increase during aging, extracellular matrix (ECM) degradation capacity also increases due to increased expression of matrix metalloproteinases (MMPs). Of the MMPs elevated with cardiac aging, MMP-9 has been extensively evaluated and its roles are reviewed here. In addition to proteolytic activity on ECM components, MMPs oversee cell signaling during the aging process by modulating cytokine, chemokine, growth factor, hormone, and angiogenic factor expression and activity. In association with elevated MMP-9, macrophage numbers increase in an age-dependent manner to regulate the ECM and angiogenic responses. Understanding the complexity of the molecular interactions between MMPs and the ECM in the context of aging may provide novel diagnostic indicators for the early detection of age-related fibrosis and cardiac dysfunction.
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Room G351-04, Jackson, MS, USA.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Meschiari
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Room G351-04, Jackson, MS, USA.
authors.forename: Osasere Kelvin
authors.initials: OK
authors.lastname: Ero
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
authors.forename: Haihui
authors.initials: H
authors.lastname: Pan
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
authors.forename: Toren
authors.initials: T
authors.lastname: Finkel
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Room G351-04, Jackson, MS, USA. mllindsey@umc.edu.|G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS, 39216-4505, USA. mllindsey@umc.edu.
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D006801:Humans; D020782:Matrix Metalloproteinases; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology; D011379:Prognosis; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D020782:Matrix Metalloproteinases
keywords: Cardiac aging; Collagen; Inflammation; Macrophage; Matrix metalloproteinases; Proteomics; Review