Macrophage Activation by Chronic P. gingivalis Endotoxin Attenuates Fibroblast Matrix Deposition Post‐Myocardial Infarction

Periodontitis is associated with an increased risk for heart failure, however the mechanisms remain unknown. Previously, we showed chronic P. gingivalis endotoxin ( Pg ) accelerated macrophage infiltration resulting in increased cardiac rupture post‐myocardial infarction (MI). We hypothesized that the early influx of macrophages would decrease myofibroblast activation leading to impaired scar formation post‐MI. Mice (4‐6 months old; n=6/sex) were infused with Pg (0.8 µg/g/day) or saline starting 28 days before and throughout the duration of MI. Expression of anti‐fibrotic cytokines (IL‐1β, Tnfα, and Ccl3) were 2‐fold higher in macrophages isolated from the infarct (LVI) of Pg mice compared to saline controls at D1 post‐MI (all p˂0.05). At D7 post‐MI, Pg exposure decreased collagen I, collagen III, fibronectin, and lysyl oxidase by 2‐fold in the LVI compared to controls (all p˂0.05). Post‐MI, fibroblasts differentiate into myofibroblasts to stimulate extracellular matrix (ECM) production. Alpha smooth muscle actin, a myofibroblast marker, decreased in the LVI of Pg mice compared to controls (p˂0.05). Our study uncovered a novel mechanism for periodontitis induced cardiac dysfunction and impaired healing post‐MI through down‐regulation of myofibroblast activation and reduced ECM deposition post‐MI.