The impact of age on cardiac function and extracellular matrix component expression in adverse post-infarction remodeling in mice

Exp Gerontol. 2019 May;119:193-202. doi: 10.1016/j.exger.2019.02.008. Epub 2019 Feb 11.


The aim of this study was to describe the potential associations of the expression of matricellular components in adverse post-infarction remodeling of the geriatric heart. In male geriatric (OM, age: 18 months) and young (YM, age: 11 weeks) OF1 mice myocardial infarction (MI) was induced by permanent ligation of the left anterior descending coronary artery. Cardiac function was evaluated by MRI. Plasma and myocardial tissue samples were collected 3d, 7d, and 32d post-MI. Age and MI were associated with impaired cardiac function accompanied by left-ventricular (LV) dilatation. mRNA expression of MMP-2 (7d: p < 0.05), TIMP-1 (7d: p < 0.05), TIMP-2 (7d: p < 0.05), Collagen-1 (3d and 7d: p < 0.05) and Collagen-3 (7d: p < 0.05) in LV non-infarcted myocardium was significantly higher in YM than in OM after MI. MMP-9 activity in plasma was increased in OM after MI (3d: p < 0.01). Tenascin-C protein levels assessed by ELISA were decreased in OM as compared to YM after MI in plasma (3d: p < 0.001, 7d: p < 0.05) and LV non-infarcted myocardium (7d: p < 0.01). Dysregulation in ECM components in non-infarcted LV might be associated and contribute to adverse LV remodeling and impaired cardiac function. Thus, targeting ECM might be a potential therapeutic approach to enhance cardiac function in geriatric patients following MI.

Keywords: Aging; Extracellular matrix remodeling; MMPs; Myocardial infarction; TIMPs; Tenascin-C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / pathology
  • Aging / physiology*
  • Animals
  • Disease Models, Animal
  • Extracellular Matrix / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / blood
  • Mice
  • Myocardial Infarction / genetics
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tenascin / blood
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Ventricular Remodeling / genetics
  • Ventricular Remodeling / physiology*


  • RNA, Messenger
  • Tenascin
  • Timp1 protein, mouse
  • Timp2 protein, mouse
  • Tissue Inhibitor of Metalloproteinase-1
  • Tnc protein, mouse
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse