title: P. gingivalis lipopolysaccharide intensifies inflammation post-myocardial infarction through matrix metalloproteinase-9.
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 28 days before performing MI, and continued to deliver PgLPS for up to 7 days 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.
authors.affiliation: San Antonio Cardiovascular Proteomics Center, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA; Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Kristine Y
authors.initials: KY
authors.lastname: DeLeon-Pennell
authors.affiliation: San Antonio Cardiovascular Proteomics Center, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA; Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Lisandra E
authors.initials: LE
authors.lastname: de Castro Brás
authors.affiliation: San Antonio Cardiovascular Proteomics Center, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA; Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Rugmani Padmanabhan
authors.initials: RP
authors.lastname: Iyer
authors.affiliation: San Antonio Cardiovascular Proteomics Center, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA; Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Dustin R
authors.initials: DR
authors.lastname: Bratton
authors.affiliation: San Antonio Cardiovascular Proteomics Center, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA; Department of Electrical and Computer Engineering, University of Texas San Antonio, San Antonio, TX 78249, USA.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Crystal M
authors.initials: CM
authors.lastname: Ripplinger
authors.affiliation: San Antonio Cardiovascular Proteomics Center, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA; Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA; Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS 39216, USA. Electronic address: mllindsey@umc.edu.
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
mesh_terms: D000818:Animals; D016866:Bacteroidaceae Infections / Q000097:blood / Q000201:enzymology / Q000276:immunology; D002465:Cell Movement; D005260:Female; D015870:Gene Expression; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000097:blood / Q000201:enzymology / Q000276:immunology*; D010510:Periodontal Diseases / Q000097:blood / Q000150:complications / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000276:immunology*
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Cardiac function; Matrix metalloproteinase-9; Myocardial infarction; Periodontal disease; Porphyromonas gingivalis; Proteomics