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Circulating Porphyromonas gingivalis lipopolysaccharide induces left ventricular dysfunction through MMP‐9 regulation of inflammation
Author(s) -
DeLeon Kristine Y,
Castro Bras Lisandra E,
Zhang Jianhua,
Lindsey Merry L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1128.14
Subject(s) - lipopolysaccharide , medicine , porphyromonas gingivalis , matrix metalloproteinase , endocrinology , saline , inflammation , ventricle , ejection fraction , cardiac function curve , chemistry , periodontitis , heart failure
Periodontal disease (PD) has been correlated to myocardial infarction (MI) however the mechanism whereby PD influences remodeling of the left ventricle (LV) is not understood. Matrix metalloproteinase (MMP)‐9 regulates LV remodeling by coordinating the inflammatory and fibrotic responses. We hypothesized that low circulating levels of P. gingivalis‐ lipopolysaccharide ( Pg ‐LPS) would induce an LV inflammatory response regulated by MMP‐9. Using echocardiography, we compared LV function in 4–7 month old wild type (WT) and MMP‐9 null mice (n≥6/group) exposed to 1 or 28 days of Pg ‐LPS (1 μg/g body weight) or saline. LV function was not affected at d1. By d28, the ejection fraction of WT+LPS significantly decreased to 57±1% compared to 67±1% for saline (p<0.05). This decrease was attenuated in null+LPS (63±1%), implicating MMP‐9 as a key regulator of cardiac function. WT+LPS LV MMP‐9 expression increased 3 fold at d1 compared to d28 and saline (both p<0.05). IL‐1α plasma levels increased at d28 in WT+LPS (187±32 pg/mL) compared to saline (110±14 pg/mL, p<0.05) and null+LPS mice (102±12 pg/mL; p<0.05). LV genes, Ccl6, Ccl9, and C3, doubled in WT+LPS at d1 compared to saline, but returned to baseline by d28. In contrast, the inflammatory response in null mice was sustained until d28. In conclusion, Pg ‐LPS induced significant changes in the inflammatory response in an MMP‐9 dependent manner causing a decrease in LV function.