Periodontal-induced chronic inflammation triggers macrophage secretion of Ccl12 to inhibit fibroblast-mediated cardiac wound healing

• DOI: 10.1172/jci.insight.94207
• Publication Date: 2017-09-20T15:00:49Z
• Authors: Kristine Y. DeLeo...; Rugmani Padmanabh...; Osasere K. Ero; Courtney A. Cates; Elizabeth R. Flynn; Presley L. Cannon; Mira Jung; De’Aries Shannon; Michael R. Garrett; William Buchanan; Michael E. Hall; Yonggang Ma; Merry L. Lindsey
• Keywords: Proinflammatory cytokine; Monocyte

Chronic inflammatory diseases, such as periodontal disease, associate with adverse wound healing in response to myocardial infarction (MI). The goal of this study was elucidate the molecular basis for impaired cardiac setting periodontal-induced chronic inflammation. Causal network analysis 168 and extracellular matrix genes revealed that inflammation induced by a subseptic dose Porphyromonas gingivalis lipopolysaccharide (LPS) exacerbated infarct expression proinflammatory cytokine Ccl12. Ccl12 prevented initiation reparative prolonging inhibiting fibroblast conversion myofibroblasts, resulting diminished scar formation. Macrophage secretion directly fibronectin collagen deposition indirectly stimulated degradation through upregulation metalloproteinase-2. In post-MI patients, circulating LPS levels strongly associated homologue monocyte chemotactic protein 1 (MCP-1). Patients ≥ endotoxin units (EU)/ml (subseptic endotoxemia) at time hospitalization had increased end diastolic systolic dimensions compared patients < EU/ml, indicating low yet pathological concentrations adversely impact left ventricle (LV) remodeling increasing MCP-1. Our provides first evidence our knowledge inhibits activation generates an unfavorable cardiac-healing environment Ccl12-dependent mechanisms.