Aging in mice increased LV dimensions and wall thickness, altered MMP/TIMP profiles suggesting increased ECM degradative capacity, and blunted fibroblast proliferation.
Aging is associated with adverse left ventricular remodeling driven by specific shifts in MMP/TIMP profiles that increase extracellular matrix degradative capacity and impair fibroblast function.
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.
Lindsey et al. (Thu,) conducted a other in Aging effects on myocardial matrix (n=61). Aging vs. Young and middle-aged mice was evaluated on LV geometry, collagen levels, MMP and TIMP abundance, and myocardial fibroblast function. Aging in mice increased LV dimensions and wall thickness, altered MMP/TIMP profiles suggesting increased ECM degradative capacity, and blunted fibroblast proliferation.
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