Abstract 15796: Systemic Exposure of Porphyromonas Gingivalis Induces Early Cardiac Dysfunction Through Activation of Cytotoxic T-Cells
Periodontal disease (PD) strongly correlates with increased mortality post-myocardial infarction (MI); however the cause is unknown. Circulating Porphyromonas gingivalis lipopolysaccharide (PgLPS) is present in over 50% of PD patients. Our previous studies revealed chronic PgLPS exposure increased systemic inflammation, which when superimposed on myocardial infarction (MI), increased and accelerated rupture of the left ventricle (LV), accelerated macrophage infiltration, and worsened cardiac function at day 7 (D7) post-MI. In this study, we hypothesized that circulating PgLPS increases the post-MI LV inflammatory response through activation of the adaptive immune response. We compared mice (4-6 months old; both sexes; n=6 survivors/group) infused with either PgLPS (0.08 μg/g/day) or saline starting at 28 days before and for the duration of MI. We used a permanent occlusion model of MI, and animals were sacrificed at D1 post-MI to examine the early inflammatory response. Proteomic profiling revealed increased levels of T-cell factors, namely interleukin (IL)-2, IL-12 and RANTES, in the LV of PgLPS exposed mice post-MI (p<0.05 vs saline). Immunofluorescence for T-cells (CD3) showed that PgLPS exposure increased T-cell infiltration (6%) compared to saline control (1%; p<0.05). Of these, 60% were CD8+ in the PgLPS group compared to 10% in the saline control (p<0.05), indicating that PgLPS exacerbated cytotoxic T-cell infiltration post-MI. Cytotoxic T-cells are activated through antigen presentation on major histocompatibility complex (MHC)-I. Post-MI, cytotoxic T-cells regulate macrophage infiltration through release of cytokines such as RANTES. To determine if cytotoxic T-cells were responsible for accelerated macrophage infiltration in PgLPS mice, MHC-I blocking antibody (MHCi, 0.2 μg/day) was given days before MI (21 days post-PgLPS initiation). Galectin-3, a macrophage marker, dropped to levels comparable to saline controls at D1 post-MI in the MHCi group (p<0.05). In conclusion, our study uncovered a novel mechanism for PD induced cardiac dysfunction through increased cytotoxic T-cell infiltration.
Author Disclosures: K.Y. DeLeon-Pennell: Research Grant; Modest; American Heart Association 13POST14350034. K.Y. DeLeon-Pennell: None. L.E. de Castro Bras: Research Grant; Modest; American Heart Association 14SDG18860050. R. Padmanabhan Iyer: Research Grant; Modest; American Heart Association 14POST18770012. E. Flynn: None. Y. Jin: None. M.L. Lindsey: Research Grant; Modest; National Institute of Health/National Heart, Lung, and Blood Institute HHSN 268201000036C (N01-HV-00244), National Institute of Health/National Heart, Lung, and Blood Institute R01HL075360, Veterans Affairs Office of Research and Development Award 5I01BX000505, HL051971, GM104357.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.