Systemic Porphyromonas gingivalis lipopolysaccharide exacerbates the inflammatory response post‐myocardial infarction through matrix metalloproteinase‐9 (897.6)

Abstract

Why periodontal disease (PD) strongly correlates with increased mortality post‐myocardial infarction (MI) is unknown. Previously, we showed P. gingivalis‐lipopolysaccharide (PgLPS) exposure increases matrix metalloproteinase (MMP)‐9 in the left ventricle (LV) of wild‐type (WT) mice. Because MMP‐9 plays a critical role post‐MI, we hypothesized that circulating PgLPS would exacerbate the LV inflammatory response post‐MI through MMP‐9. We compared WT and MMP‐9 null mice (3‐7 months old; n=12 survivors/group) infused with either PgLPS (0.08 µg/g/day) or saline for 28 days before and throughout the duration of MI. PgLPS increased rupture rate (rupture/total deaths) in WT (7/7) compared to saline controls (6/15) and was attenuated in Null (1/2). Echocardiography showed LV wall thinning increased at d7 post‐MI in WT (0.61±0.05 mm) compared to d0 (0.84±0.03 mm; p˂0.05). This effect was amplified by PgLPS in WT (0.44±0.04 mm) and attenuated in Null (0.50±0.04 mm; p˂0.05 for both). Plasma proteomics showed MMP‐9, macrophage inflammatory protein‐1β, ‐1γ, monocyte chemotactic protein‐1, and ‐3 increased in WT post‐MI and intensified by PgLPS suggesting amplified inflammatory response. This effect was attenuated by MMP‐9 deletion. In conclusion, circulating PgLPS exacerbates LV inflammation post‐MI through a MMP‐9 mechanism, resulting in a greater extent of LV dysfunction.Grant Funding Source: Supported by AHA POST14350034; HHSN 268201000036C; R01HL075360; VA 5I01BX000505; HL051971