OBJECTIVE: To evaluate the effects of aging on left ventricular (LV) geometry, collagen levels, matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) abundance, and myocardial fibroblast function. METHODS: Young (3-month-old; n=28), middle-aged (MA; 15-month-old; n=17), and old (23-month-old; n=16) CB6F1 mice of both sexes were used in this study. Echocardiographic parameters were measured; collagen, MMP, and TIMP levels were determined for both the soluble and insoluble protein fractions; and fibroblast function was evaluated. RESULTS: LV end-diastolic dimensions and wall thickness increased in both MA and old mice, accompanied by increased soluble protein and decreased insoluble collagen. Immunoblotting revealed differential MMP/TIMP profiles. Compared to MA levels, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-14 increased, and TIMP-3 and TIMP-4 decreased in the insoluble fraction of old mice, suggesting increased extracellular matrix (ECM) degradative capacity. Fibroblast proliferation was blunted with age. CONCLUSION: This study, for the first time, identified specific differences in cellular and extracellular processes that likely contribute to age-dependent ECM remodeling.
OBJECTIVE: To evaluate the effects of aging on left ventricular (LV) geometry, collagen levels, matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) abundance, and myocardial fibroblast function. METHODS: Young (3-month-old; n=28), middle-aged (MA; 15-month-old; n=17), and old (23-month-old; n=16) CB6F1 mice of both sexes were used in this study. Echocardiographic parameters were measured; collagen, MMP, and TIMP levels were determined for both the soluble and insoluble protein fractions; and fibroblast function was evaluated. RESULTS: LV end-diastolic dimensions and wall thickness increased in both MA and old mice, accompanied by increased soluble protein and decreased insoluble collagen. Immunoblotting revealed differential MMP/TIMP profiles. Compared to MA levels, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-14 increased, and TIMP-3 and TIMP-4 decreased in the insoluble fraction of old mice, suggesting increased extracellular matrix (ECM) degradative capacity. Fibroblast proliferation was blunted with age. CONCLUSION: This study, for the first time, identified specific differences in cellular and extracellular processes that likely contribute to age-dependent ECM remodeling.
Authors: Alan J Mouton; Osvaldo J Rivera Gonzalez; Amanda R Kaminski; Edwin T Moore; Merry L Lindsey Journal: Pharmacol Res Date: 2018-10-28 Impact factor: 7.658
Authors: Jing Lin; Harrison B Davis; Qiuxia Dai; Youn-Min Chou; Teresa Craig; Carmen Hinojosa-Laborde; Merry L Lindsey Journal: Hypertens Res Date: 2008-06 Impact factor: 3.872
Authors: Amy D Bradshaw; Catalin F Baicu; Tyler J Rentz; An O Van Laer; D Dirk Bonnema; Michael R Zile Journal: Am J Physiol Heart Circ Physiol Date: 2009-12-11 Impact factor: 4.733
Authors: D Dirk Bonnema; Carson S Webb; Weems R Pennington; Robert E Stroud; Amy E Leonardi; Leslie L Clark; Catherine D McClure; Laura Finklea; Francis G Spinale; Michael R Zile Journal: J Card Fail Date: 2007-09 Impact factor: 5.712