<i>Porphyromonas Gingivalis</i> Elevated High-Mobility Group Box 1 Levels After Myocardial Infarction in Mice

Abstract

SummaryHigh mobility group box 1 (HMGB1) is a nuclear protein released from necrotic cells, inducing inflammatory responses. Epidemiological studies suggested a possible association between periodontitis and cardiovascular diseases (CVDs). Due to tissue damage and necrosis of cardiac cells following myocardial infarction (MI), HMGB1 is released, activating an inflammatory reaction. However, it remains unclear whether periodontitis is also involved in myocardial damage. The purpose of this study was to determine the effect of the periodontal pathogen Porphyromonas gingivalis (P.g.) after MI in mice.C57BL/6J wild type mice in post-MI were inoculated with P.g. in the infected group (P.g.-inoculated MI group) and with phosphate buffer saline (PBS) in the control group (PBS-injected MI group). Plasma samples and twelve tissue samples from mice hearts after MI were obtained. We determined the expression of HMGB1 by ELISA and immunohistochemistry.The level of HMGB1 protein in the P.g.-inoculated MI group was significantly higher than in the PBSinjected MI group on day 5, but not on day 14. Immunohistochemistry analysis revealed that HMGB1 was mainly expressed in cardiomyocytes, immune cells, and vascular endothelial cells in the PBS-injected MI group, while HMGB1 was seen broadly in degenerated cardiomyocytes, extracellular fields, immune cells, and vascular endothelial cells in the P.g.-inoculated MI group. A significant increase in the number of HMGB1 positive cells was observed in the P.g.-inoculated MI group compared to the PBS-injected MI group.Infection with P.g. after MI enhanced myocardial HMGB1 expression. There is a possible relationship between periodontitis and post-infarction myocardial inflammation through HMGB-1.(Int Heart J 2017; 58: 762-768)

Short-term effect of ligature-induced periodontitis on cardiovascular variability and inflammatory response in spontaneously hypertensive rats

“…These functions affect neutrophil chemotaxis and activation, and endothelial cell function. In fact, chronic inflammation caused by PD is involved in systemic effects in distant organs, such as the heart [61][62][63][64][65]. In the current study the hearts from SHR with PD showed increased pro-inflammatory cytokine IL-1β concentrations.…”

Cardiovascular and Autonomic Dysfunction in Murine Ligature-Induced Periodontitis

“…The presence of these cytokines, especially IL-17 and IL-6, are strongly associated with cardiovascular alterations 8,44,45 . Corroborating these findings, other experimental studies in mice have also shown high levels of inflammatory mediators in the heart, following systemic administration of bacterial components or periodontal bacteria 42,[46][47][48][49][50][51] , although few studies evaluated the heart cytokines in ligature model. These inflammatory mediators could cause derangement of the heart and autonomic dysfunction; for instance, IL-17 has been crucial to myocarditis caused by Porphyromonas gingivalis 46 .…”

Porphyromonas gingivalis and Its Systemic Impact: Current Status

“…It promotes cardiomyocyte apoptosis by activating Bax and increases matrix metalloproteinase-9 (MMP-9) activity by enhancing oxidative stress, thereby exerting a strongly detrimental effect on the healing process of the infarcted myocardium and subsequently leading to cardiac rupture after MI [ 51 ]. Additionally, P. gingivalis may aggravate myocardial injury after MI by elevating the expression of high mobility group box 1, a nuclear protein from necrotic cells that can induce an inflammatory response [ 52 ]. Lastly, P. gingivalis -associated production of IL-17A might play an essential role in the pathology of MI, as IL-17A was found to exacerbate ventricular remodeling after acute MI in mice [ 50 ].…”