P. gingivalis lipopolysaccharide intensifies inflammation post-myocardial infarction through matrix metalloproteinase-9

Kristine Y. DeLeon-Pennell, Lisandra E. de Castro Brás, Rugmani Padmanabhan Iyer, Dustin R. Bratton, Yu Fang Jin, Crystal M. Ripplinger, Merry L. Lindsey

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Periodontal disease (PD) strongly correlates with increased mortality post-myocardial infarction (MI); however, the underlying mechanisms are unknown. Matrix metalloproteinase (MMP)-9 levels directly correlate with dysfunction and remodeling of the left ventricle (LV) post-MI. Post-MI, MMP-9 is produced by leukocytes and modulates inflammation. We have shown that exposure to Porphyromonas gingivalis lipopolysaccharide (PgLPS), an immunomodulatory molecule identified in PD patients, increases LV MMP-9 levels in mice and leads to cardiac inflammation and dysfunction. The aim of the study was to determine if circulating PgLPS exacerbates the LV inflammatory response post-MI through MMP-9 dependent mechanisms. We exposed wild type C57BL/6J and MMP-9-/- mice to PgLPS (ATCC 33277) for a period of 28days before performing MI, and continued to deliver PgLPS for up to 7days post-MI. We found systemic levels of PgLPS 1) increased MMP-9 levels in both plasma and infarcted LV resulting in reduced wall thickness and increased incidence of LV rupture post-MI and 2) increased systemic and local macrophage chemotaxis leading to accelerated M1 macrophage infiltration post-MI and decreased LV function. MMP-9 deletion played a protective role by attenuating the inflammation induced by systemic delivery of PgLPS. In conclusion, MMP-9 deletion has a cardioprotective role against PgLPS exposure, by attenuating macrophage mediated inflammation.

Original languageEnglish (US)
Pages (from-to)218-226
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume76
DOIs
StatePublished - Nov 1 2014

Keywords

  • Cardiac function
  • Matrix metalloproteinase-9
  • Myocardial infarction
  • Periodontal disease
  • Porphyromonas gingivalis
  • Proteomics

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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