Periodontal bacteria aggravate experimental autoimmune myocarditis in mice

Ashigaki, Norihiko; Suzuki, Jun–ichi; Ogawa, Masahito; Watanabe, Ryoji; Aoyama, Norio; Kobayashi, Naho; Hanatani, Tomoya; Sekinishi, Asuka; Zempo, Hirofumi; Tada, Yuko; Takamura, Chisato; Wakayama, Kouji; Hirata, Yasunobu; Nagai, Ryozo; Izumi, Yuichi; Isobe, Mitsuaki

doi:10.1152/ajpheart.00634.2012

Cited by 14 publications

(9 citation statements)

References 44 publications

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“…This increase was accompanied by a decrease in fractional shortening, suggesting that Pg -LPS exposure induces LV dysfunction through MMP-9 effects on systolic function. This finding is in conflict with findings published in Ashigaki et al, however in this study the exposure to P. gingivalis is only 14 days compared to our study which exposed the mice for 28 days to Pg -LPS (Ashigaki et al 2013). This suggests that longer exposure time may be needed to induce cardiac dysfunction through increased MMP-9.…”

Section: Discussioncontrasting

confidence: 99%

CirculatingPorphyromonas gingivalislipopolysaccharide resets cardiac homeostasis in mice through a matrix metalloproteinase-9-dependent mechanism

2013

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Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) circulates systemically in over 50% of periodontal disease (PD) patients and is associated with increased matrix metalloproteinase (MMP)-9. We hypothesized that low systemic Pg-LPS would stimulate an inflammatory response in the left ventricle (LV) through MMP-9, leading to a decrease in cardiac function. Wild type (WT) and MMP-9 Null mice (4-7 months old) were exposed for 1 or 28 days to low dose Pg-LPS or saline (n≥6/group). MMP-9 significantly increased in WT LV at 1 and 28 days of exposure, compared to control (p<0.05 for both). Fractional shortening decreased subtly yet significantly in WT by d28 (31±1%) compared to control (35±1%; p<0.05), and this decrease was attenuated in Null (34±1%). Plasma cardiac troponin I levels were elevated in WT mice at d28. Macrophage related factors increased over 2-fold in WT plasma and LV after d1 (monocyte chemoattractant protein-5, macrophage inflammatory protein (MIP)-1α, MIP-1γ, stem cell factor, Ccl12, Ccl9, Il8rb, Icam1, Itgb2, and Spp1; all p<0.05), indicating a moderate inflammatory response. Levels returned to baseline by d28, suggesting tolerance to Pg-LPS. In contrast, macrophage related factors remained elevated in d28 Null, indicating a sustained defense against Pg-LPS stimulation. Consistent with these findings, LV macrophage numbers increased in both groups at d1 and returned to baseline by d28 in the WT only. Major histocompatibility complex (MCH) II remained elevated in the Null group at d28, confirming Pg-tolerance in the WT. Interestingly Il-1α, a regulator of macrophage immunosuppression, increased in the plasma of WT only at d28, suggesting Il-1α plays a role in tolerance in a MMP-9 dependent manner. In conclusion, circulating Pg-LPS induced tolerance in WT, resulting in significant LV changes and subtle cardiac dysfunction. MMP-9 played a major role in the regulation of chronic systemic inflammation and associated cardiac dysfunction.

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Section: Discussioncontrasting

confidence: 99%

CirculatingPorphyromonas gingivalislipopolysaccharide resets cardiac homeostasis in mice through a matrix metalloproteinase-9-dependent mechanism

2013

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“…Moreover, despite limitations in clinical research, studies have shown the association between the severity of periodontitis and cardiac hypertrophy in humans 40,41 . Besides, experimental studies with the administration of Porphyromonas gingivalis, one of the major bacteria involved in periodontitis, demonstrated the development of cardiac hypertrophy and fibrosis 42,43 . In addition, in the experimental model of Aggregatibacter actinomycetemcomitans infection, there was also an increase in myocardial hypertrophy, fibrosis, and arteriosclerosis in the transverse aortic constriction model 42 .…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular and Autonomic Dysfunction in Murine Ligature-Induced Periodontitis

Ribeiro

Santos-Júnior

Luiz

et al. 2020

Sci Rep

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the present study examined the hemodynamics [arterial pressure (Ap), Ap variability (ApV), heart rate (HR), and heart rate variability (HRV)], cardiac function (echocardiographycally), and myocardial inflammation in Balb/c mice submitted to Periodontitis, through the ligation of the left first molar, or Sham surgical procedure. The first protocol indicated that the AP was similar (136 ± 2 vs. 132 ± 3 mmHg in Sham), while the HR was higher in mice with Periodontitis (475 ± 20 vs. 412 ± 18 bpm in Sham), compared to their Sham counterparts. The APV was higher in mice with Periodontitis when evaluated in the time domain (4.5 ± 0.3 vs. 3.4 ± 0.2 mmHg in Sham), frequency domain (power of the LF band of systolic AP), or through symbolic analysis (patterns 0V + 1V), indicating a sympathetic overactivity. The HRV was similar in the mice with Periodontitis, as compared to their Sham counterparts. In the second protocol, the mice with Periodontitis showed decreased cardiac output (10 ± 0.8 vs. 15 ± 1.4 mL/ min in Sham) and ejection fraction (37 ± 3 vs. 47 ± 2% in Sham) associated with increased myocardial cytokines (Interleukin-17, Interleukin-6, and Interleukin-4). This study shows that experimental periodontitis caused cardiac dysfunction, increased heart cytokines, and sympathetic overactivity, in line with epidemiological studies indicating an increased risk of cardiovascular events in clinical periodontitis. Periodontitis is caused by a chronic inflammatory response to a periodontal biofilm that deranges the supporting tissues around the teeth (alveolar bone, periodontal ligament, and cementum), causing dental loss 1. This inflammatory disease represents a major public health problem, with an estimated prevalence of over 790 million people worldwide 2,3. Of note, more than 700 species of bacteria are estimated in the oral cavity forming the dental biofilm 4,5. Biofilms can release biologically active products, including bacterial lipopolysaccharides, chemotactic mediators, protein toxins, and organic acids. These active products elicit different components of innate and adaptive immunity 6 followed by the production of inflammatory mediators, mainly cytokines produced by immune cells 7. These cytokines, including interleukin (IL)-17, IL-6, IL-4, and other inflammatory mediators, such as C-reactive protein, are released in response to the stimuli induced by the dental biofilm 8. Different rodent models of periodontal disease have been described to investigate the pathophysiology of this inflammatory disease and accompanying complications 9,10. Nevertheless, the placement of a ligature around a molar tooth is one of the most widely used model 11. Indeed, ligatures around the posterior teeth mimic human periodontitis, leading to local inflammatory cell accumulation, apical migration of junctional epithelium, and bone loss 9,12,13. Moreover, the structure of the dental gingival area in the rodent is quite similar to that exhibited by humans 14. Recent studies have proven that the harmful effects of periodontitis are not re...

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“…Complementary DNA was prepared with a reverse transcriptase-polymerase chain reaction (RT-PCR) kit (QIAGEN, Tokyo, Japan) 27 . The PCR was performed with a PCR-kit in the presence of oligo-primers for transforming growth factor beta 1 ( Tgfb1 , Mm01178820_m1) and collagen1a1 ( Col1a1 , Mm01302043_g1).…”

Section: Methodsmentioning

confidence: 99%

Influence of periostin-positive cell-specific Klf5 deletion on aortic thickening in DOCA-salt hypertensive mice

et al. 2016

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Chronic hypertension causes vascular remodeling that is associated with an increase of periostin (postn) positive cells, including fibroblasts and smooth muscle cells. Krüppel-like factor (KLF) 5, a transcription factor, is also observed in vascular remodeling, however, it is unknown what role KLF5 plays in postn positive cells during vascular remodeling induced by deoxycorticosterone acetate (DOCA)-salt. We used postn positive cell-specific Klf5 deficient (Klf5PostnKO: Klf5flox/flox;PostnCre/−) mice and wild type (WT: Klf5flox/flox;Postn−/−) mice. We implanted a DOCA pellet and provided drinking water that containing 0.9% NaCl for eight-weeks. The DOCA-salt treatment induced hypertension in both genotype groups, as observed by the increase in systolic blood pressure. In WT, DOCA-salt treatment increased the aortic medial area compared to non-treated controls. Similarly, Tgf1b was overexpressed in the aortas of DOCA-salt treated WT mice compared to controls. Immunofluorescence staining revealed that fibroblast specific protein 1 (FSP1)+-α smooth muscle actin (αSMA)+ myofibroblast exist in the medial area of WT aorta after DOCA-salt intervention. Importantly, these changes were not observed in the Klf5PostnKO animals. In conclusion, the results of this study suggest that the presence of KLF5 on postn positive cells contributes to the pathogenesis of aortic thickening induced by DOCA-salt hypertension.

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Periodontal bacteria aggravate experimental autoimmune myocarditis in mice

Cited by 14 publications

References 44 publications

CirculatingPorphyromonas gingivalislipopolysaccharide resets cardiac homeostasis in mice through a matrix metalloproteinase-9-dependent mechanism

CirculatingPorphyromonas gingivalislipopolysaccharide resets cardiac homeostasis in mice through a matrix metalloproteinase-9-dependent mechanism

Cardiovascular and Autonomic Dysfunction in Murine Ligature-Induced Periodontitis

Influence of periostin-positive cell-specific Klf5 deletion on aortic thickening in DOCA-salt hypertensive mice

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