Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function

Merry L. Lindsey, Danielle K. Goshorn, Christina E. Squires, G. Patricia Escobar, Jennifer W. Hendrick, Joseph T. Mingoia, Sarah E. Sweterlitsch, Francis G. Spinale

Research output: Contribution to journalReview article

116 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)410-419
Number of pages10
JournalCardiovascular research
Volume66
Issue number2
DOIs
StatePublished - May 1 2005

Keywords

  • Extracellular matrix
  • Matrix metalloproteinase
  • Matrix remodeling
  • Tissue inhibitor of metalloproteinase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function'. Together they form a unique fingerprint.

  • Cite this

    Lindsey, M. L., Goshorn, D. K., Squires, C. E., Escobar, G. P., Hendrick, J. W., Mingoia, J. T., Sweterlitsch, S. E., & Spinale, F. G. (2005). Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function. Cardiovascular research, 66(2), 410-419. https://doi.org/10.1016/j.cardiores.2004.11.029