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

Cardiovasc Res. 2005 May 1;66(2):410-9. doi: 10.1016/j.cardiores.2004.11.029. Epub 2004 Dec 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / physiology*
  • Animals
  • Cell Proliferation
  • Collagen / metabolism
  • Electrocardiography
  • Female
  • Fibroblasts / cytology
  • Immunoblotting
  • Male
  • Matrix Metalloproteinase 3 / analysis
  • Matrix Metalloproteinase 8 / analysis
  • Matrix Metalloproteinase 9 / analysis
  • Matrix Metalloproteinases / analysis
  • Matrix Metalloproteinases / metabolism*
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / analysis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myocardium / cytology
  • Myocardium / enzymology*
  • Tissue Inhibitor of Metalloproteinase-3 / analysis
  • Tissue Inhibitor of Metalloproteinases / analysis
  • Tissue Inhibitor of Metalloproteinases / metabolism*
  • Ventricular Function, Left / physiology


  • Tissue Inhibitor of Metalloproteinase-3
  • Tissue Inhibitor of Metalloproteinases
  • tissue inhibitor of metalloproteinase-4
  • Collagen
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9