title: Exercise training reduces fibrosis and matrix metalloproteinase dysregulation in the aging rat heart.
abstract: Aging impairs function in the nonischemic heart and is associated with mechanical remodeling. This process includes accumulation of collagen (i.e., fibrosis) and dysregulation of active matrix metalloproteinases (MMPs). Exercise training (ET) improves cardiac function, but the pathways of protection remain poorly understood. Young (3 mo) and old (31 mo) FBNF1 rats were assigned into sedentary and exercise groups, with ET group rats training on a treadmill 45 min/d, 5 d/wk for 12 wk. Nonlinear optical microscopy (NLOM), histology, immunohistochemistry (IHC), and Western blot analyses were performed on the left ventricle and septum. NLOM, IHC, and histological imaging revealed that ET reduced age-associated elevation of collagen type I fibers. Active MMP-1, active MMP-2, and MMP-14 in the ECM fraction of the left ventricle were reduced by aging, an effect abrogated by ET. Tissue inhibitor of MMP (TIMP-1) was elevated with age but protected by ET. Transforming growth factor-β (TGF-β), upstream regulator of TIMP-1, increased with age but was attenuated by ET. Therefore, exercise training could protect the aging heart against dysregulation of MMPs and fibrosis by suppressing elevation of TIMP-1 and TGF-β.
authors.affiliation: Redox Biology and Cell Signaling Laboratory, Department of Health and Kinesiology, Texas A&M University, College Station, TX 77843-4243, USA.
authors.forename: Hyo-Bum
authors.initials: HB
authors.lastname: Kwak
authors.forename: Jong-hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Kumar
authors.initials: K
authors.lastname: Joshi
authors.forename: Alvin
authors.initials: A
authors.lastname: Yeh
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Martinez
authors.forename: John M
authors.initials: JM
authors.lastname: Lawler
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D005355:Fibrosis; D006331:Heart Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1; D053511:Matrix Metalloproteinase 14