Matrix metalloproteinase-28 deletion amplifies inflammatory and extracellular matrix responses to cardiac aging

Microsc Microanal. 2012 Feb;18(1):81-90. doi: 10.1017/S1431927611012220. Epub 2011 Dec 8.


To determine if matrix metalloproteinase (MMP)-28 mediates cardiac aging, wild-type (WT) and MMP-28-/- young (7 ± 1 months, n = 9 each) and old (20 ± 2 months, n = 7 each) female mice were evaluated. MMP-28 expression in the left ventricle (LV) increased 42% in old WT mice compared to young controls (p < 0.05). By Doppler echocardiography, LV function declined at 20 ± 2 months of age for both groups. However, dobutamine stress responses were similar, indicating that cardiac reserve was maintained. Plasma proteomic profiling revealed that macrophage inflammatory protein (MIP)-1 α, MIP-1β and MMP-9 plasma levels did not change in WT old mice but were significantly elevated in MMP-28-/- old mice (all p < 0.05), suggestive of a higher inflammatory status when MMP-28 is deleted. RT2-PCR gene array and immunoblotting analyses demonstrated that MIP-1α and MMP-9 gene and protein levels in the LV were also higher in MMP-28-/- old mice (all p < 0.05). Macrophage numbers in the LV increased similarly in WT and MMP-28-/- old mice, compared to respective young controls (both p < 0.05). Collagen content was not different among the WT and MMP-28-/- young and old mice. In conclusion, LV inflammation increases with age, and MMP-28 deletion further elevates inflammation and extracellular matrix responses, without altering macrophage numbers or collagen content.

Publication types

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

MeSH terms

  • Aging*
  • Animals
  • Echocardiography, Doppler
  • Extracellular Matrix / metabolism*
  • Female
  • Gene Deletion
  • Heart / physiology*
  • Heart / physiopathology
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Macrophages / metabolism
  • Matrix Metalloproteinases, Secreted / deficiency*
  • Matrix Metalloproteinases, Secreted / metabolism*
  • Mice
  • Mice, Knockout
  • Myocarditis / pathology
  • Myocarditis / physiopathology
  • Myocardium / pathology*
  • Plasma / chemistry


  • Matrix Metalloproteinases, Secreted
  • Mmp28 protein, mouse