Active Invasion of Oral and Aortic Tissues by Porphyromonas gingivalis in Mice Causally Links Periodontitis and Atherosclerosis

Abstract

Atherosclerotic vascular disease is a leading cause of myocardial infarction and cerebrovascular accident, and independent associations with periodontal disease (PD) are reported. PD is caused by polymicrobial infections and aggressive immune responses. Genomic DNA of Porphyromonas gingivalis, the best-studied bacterial pathogen associated with severe PD, is detected within atherosclerotic plaque. We examined causal relationships between chronic P. gingivalis oral infection, PD, and atherosclerosis in hyperlipidemic ApoEnull mice. ApoEnull mice (n = 24) were orally infected with P. gingivalis for 12 and 24 weeks. PD was assessed by standard clinical measurements while the aorta was examined for atherosclerotic lesions and inflammatory markers by array. Systemic inflammatory markers serum amyloid A, nitric oxide, and oxidized low-density lipoprotein were analyzed. P. gingivalis infection elicited specific antibodies and alveolar bone loss. Fluorescent in situ hybridization detected viable P. gingivalis within oral epithelium and aorta, and genomic DNA was detected within systemic organs. Aortic plaque area was significantly increased in P. gingivalis-infected mice at 24 weeks (P<0.01). Aortic RNA and protein arrays indicated a strong Th2 response. Chronic oral infection with P. gingivalis results in a specific immune response, significant increases in oral bone resorption, aortic inflammation, viable bacteria in oral epithelium and aorta, and plaque development.

Cerebral Oxidative Stress and Microvasculature Defects in TNF-α Expressing Transgenic and Porphyromonas gingivalis-Infected ApoE–/– Mice

“…ApoE -/-male mice (strain B6.129P2-Apoe tm1Unc/J , N = 12) were sham-infected or monoinfected for 12 weeks via the oral route, with the P. gingivalis FDC 381 strain (5×10 9 bacteria / mL), as described previously [35]. …”

Apolipoprotein E Related Co-Morbidities and Alzheimer’s Disease

“…This primary environmental risk factor (infection) has the potential for pathogenic interplay in the hetero/homozygous apoε4 genotype via initiation of an intrinsic cascade of risk factors (infection>inflammation) for dyslipidaemia. Another common feature of all the mono and polyinfected experiments in ApoE −/− mice [71,75] was the abundant expression of NPY gene in vascular tissues [75]. This suggests an intricate relationship of NPY gene and chronic infections with possible manifestation for the development of insulin resistance as discussed below.…”

“…These studies have demonstrated bacterial colonization and progression of PD in the ApoE −/− mouse model (bacterial invasion, gingival inflammation, apical migration of junctional epithelium, alveolar bone resorption, and intra-bony defects). By comparing control to infected mice, a significantly elevated IgG response to P. gingivalis and T. denticola and T forsythia mono-infections as well as in the polymicrobial infections was recorded [70][71][72]. The 8 humoral response generated in all of the infected groups, provides further evidence of a stable response to PD pathogens as well as manifestation of chronic inflammation [70][71][72].…”

“…nucleatum] [70][71][72][73], both as a polymicrobial infection and as monoinfections [71][72][73][74]. These studies have demonstrated bacterial colonization and progression of PD in the ApoE −/− mouse model (bacterial invasion, gingival inflammation, apical migration of junctional epithelium, alveolar bone resorption, and intra-bony defects).…”

“…By comparing control to infected mice, a significantly elevated IgG response to P. gingivalis and T. denticola and T forsythia mono-infections as well as in the polymicrobial infections was recorded [70][71][72]. The 8 humoral response generated in all of the infected groups, provides further evidence of a stable response to PD pathogens as well as manifestation of chronic inflammation [70][71][72]. This primary environmental risk factor (infection) has the potential for pathogenic interplay in the hetero/homozygous apoε4 genotype via initiation of an intrinsic cascade of risk factors (infection>inflammation) for dyslipidaemia.…”