Copyright © 2004, European Society of Cardiology
Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function
aDivision of Cardiothoracic Surgery Research, Room 629, Strom Thurmond Research Building, 770 MUSC Complex, Medical University of South Carolina, 114 Doughty Street, P.O. Box 250778, Charleston, SC 29425, United States
bRalph A. Johnson Veterans Administration Medical Center, Charleston, SC 29425, United States
* Corresponding author. Tel.: +-1 843 876 5186; fax: +-1 843 876 5187. Email address: lindseml{at}musc.edu
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.
KEYWORDS Matrix metalloproteinase; Tissue inhibitor of metalloproteinase; Extracellular matrix; Matrix remodeling
Time for primary review 28 days
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