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

Yonggang Ma, Ying Ann Chiao, Jianhua Zhang, Anne M. Manicone, Yu Fang Jin, Merry L. Lindsey

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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. RT 2-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.

Original languageEnglish (US)
Pages (from-to)81-90
Number of pages10
JournalMicroscopy and Microanalysis
Volume18
Issue number1
DOIs
StatePublished - Feb 1 2012

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deletion
Aging of materials
matrices
mice
macrophages
Macrophages
proteins
Proteins
collagens
Collagen
genes
Metalloproteases
Genes
Plasmas
echocardiography
Echocardiography

Keywords

  • MMP-28
  • cardiac aging
  • collagen
  • extracellular matrix
  • inflammation
  • left ventricle
  • macrophage
  • mice

ASJC Scopus subject areas

  • Instrumentation

Cite this

Matrix metalloproteinase-28 deletion amplifies inflammatory and extracellular matrix responses to cardiac aging. / Ma, Yonggang; Chiao, Ying Ann; Zhang, Jianhua; Manicone, Anne M.; Jin, Yu Fang; Lindsey, Merry L.

In: Microscopy and Microanalysis, Vol. 18, No. 1, 01.02.2012, p. 81-90.

Research output: Contribution to journalArticle

Ma, Yonggang ; Chiao, Ying Ann ; Zhang, Jianhua ; Manicone, Anne M. ; Jin, Yu Fang ; Lindsey, Merry L. / Matrix metalloproteinase-28 deletion amplifies inflammatory and extracellular matrix responses to cardiac aging. In: Microscopy and Microanalysis. 2012 ; Vol. 18, No. 1. pp. 81-90.
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