Streptococci from the mouth which enter the bloodstream during dental work have long been known to cause endocarditis. And, "early immunization experiments with oral streptococcal organisms (especially s mutans for vaccination against caries) resulted in the production of autoimmune antivascular and anticardiac cross-reactive immunoglobulins. Recently, landmark studies by Herzberg et al have identified the cross-reactive immunodeterminants responsible. S sanguis contains an outer membrane associated protein... which is identical to the platelet-interactive domain of Type I and Type II collagens. This bacterial protein thus presents or 'mimics' the normal platelet receptor that initiates thrombus formation. Type III collagen is in the wall and basement membrane of vessels and is normally covered with endothelial cells, which serves to mask these platelet binding receptor sequences from circulating blood cells. Trauma or other noxious stimuli which expose these receptors and thereby provide an important signal to initiate hemostasis or thrombosis. Herzberg et al also report that Porphyromonas gingivalis (a gram-negative periodontal pathogen) has properties similar to S sanguis. Taken together, these findings suggest that oral organisms may serve as a thromboembolic trigger." (Dental infections and atherosclerosis. JD Beck, J Pankow, HA Tyroler, S Offenbacher. Am Heart J 1999;138:S528-S533.)Beck - Am Heart J 1999 abstract / PubMed
"Patients who experience acute MI are nearly three times more likely to have periodontitis than healthy persons, according to data presented here Monday at the American Heart Association's Scientific Sessions." (Re: E Deliagyris et al. Reuters Medical News via Medscape, 2000 Nov 14.) In the news report on Gannett / NBC WGRZ Channel 2, Buffalo, New York, Deliagyris said, "'We know a lot of risk factors for heart attacks, including high blood pressure, high cholesterol, diabetes, and cigarette smoking, but all those combined only explain about two-thirds of heart attacks,' Deliagyris said. 'Since about a third of people who suffer heart attacks don't have those risk factors, there's a wide search going on for other conditions that may contribute to increased risk.'" This is the official lie of the anti-smoking establishment. The deceit is in blaming smoking for heart disease that's really caused by infection.
Periodontal infections and cardiovascular disease -- how strong is the association? GC Armitage. Oral Dis 2000 Nov;6(6):335-350. Review.Armitage - Oral Dis 2000 abstract / PubMed
Systemic release of endotoxins induced by gentle mastication: association with periodontitis severity. SO Geerts, M Nys, MP De, J Charpentier, A Albert, V Legrand, EH Rompen. J Periodontol 2002 Jan;73(1):73-78. "This finding suggests that a diseased periodontium can be a major and underestimated source of chronic, or even permanent, release of bacterial pro-inflammatory components into the bloodstream." (News re Geerts et al.: Infected gums leak toxins into bloodstream. By Melissa Schorr. Reuters Health Information - Medscape 2002 Feb. 8. Link died.)Geerts - J Periodontol 2002 abstract / PubMed
Periodontal infections and coronary heart disease: role of
periodontal bacteria and importance of total pathogen burden in the
Coronary Event and Periodontal Disease (CORODONT) study. A Spahr, E
Klein, N Khuseyinova, C Boeckh, R Muche, M Kunze, D Rothenbacher, G
Pezeshki, A Hoffmeister, W Koenig. Arch Intern Med 2006 Mar
13;166(5):554-559. 263 CHD patients and 526 controls. "In multivariable
analyses, we found a statistically significant association between the
periodontal pathogen burden (log10 of the sum of all pathogens) (odds
ratio [OR], 1.92; 95% confidence interval [CI], 1.34-2.74;
or the number of A actinomycetemcomitans in periodontal pockets (log10)
(OR, 2.70; 95% CI, 1.79-4.07; P<.001) and the presence of CHD.
addition, a statistically significant association between an increase
in mean CPITN score by 1 and the presence of CHD (OR, 1.67; 95% CI,
1.08-2.58; P = .02) was observed."
Bacterial Profile and Burden of Periodontal Infection in
With a Diagnosis of Acute Coronary Syndrome. S Renvert, T Pettersson, O
Ohlsson, GR Persson. J Periodontol 2006 Jul;77(7):1110-1119. In
161 surviving acute coronary patients and 161 controls, "Total oral
bacterial load was higher in the subjects with ACS (mean difference:
17.4 x 10(5); SD: 10.8; 95% confidence interval [CI]: 4.2 to 17.4; P
<0.001), and significant for 26 of 40 species including
Porphyromonas gingivalis, Tannerella forsythensis, and Treponema
denticola." Also: Study Supports Findings That Periodontal Bacteria May
Be Linked to Heart Disease. SOURCE: American Academy of Periodontology.
DGNews, July 19, 2006. "The amount of oral bacteria was two times
higher in the ACS group for the combination of the bacteria
streptococci species, P. gingivalis, T. forsythia and T. denticola.
Specifically, the findings suggest that T. denticola, T. forsythia and
streptococci species are bacteria in a shared infectious etiology for
periodontitis and ACS."
Detection of cariogenic Streptococcus mutans in extirpated
valve and atheromatous plaque specimens. K Nakano, H Inaba, R Nomura, H
Nemoto, M Takeda, H Yoshioka, H Matsue, T Takahashi, K Taniguchi, A
Amano, T Ooshima. J Clin Microbiol 2006 Sep;44(9):3313-3317. 35 heart
valve and 27 atheromatous plaque clinical specimens, as well as 32
dental plaque specimens from the same subjects, analyzed by PCR.
"Streptococcus mutans was frequently detected in the heart valve (69%)
and atheromatous plaque (74%) specimens, while other bacterial species,
including those related to periodontitis, were detected with much lower
Evaluation of the incidence of periodontitis-associated
the atherosclerotic plaque of coronary blood vessels. M Zaremba, R
Górska, P Suwalski, J Kowalski. J Periodontol 2007
Feb;78(2):322-327. "In 13 of 20 patients, the pathogens most frequently
found in severe chronic periodontitis were also found in coronary
vessels. In 10 cases, those species of bacteria were also present in
atherosclerotic plaque. The most frequently identified bacteria were
Porphyromonas gingivalis and Treponema denticola."
Treatment of periodontitis and endothelial function. MS
D'Aiuto, L Nibali, A Donald, C Storry, M Parkar, J Suvan, AD
Hingorani, P Vallance, J Deanfield. New Engl J Med 2007 Mar
1;356(9):911-920. A randomized clinical trial of 120 patients with
severe periodontal disease, assigned to community-based periodontal
care (59 patients) or intensive periodontal treatment (61). Endothelial
function, as assessed by measurement of the diameter of the brachial
artery during flow (flow-mediated dilatation), and inflammatory
biomarkers and markers of coagulation and endothelial activation were
evaluated before treatment and 1, 7, 30, 60, and 180 days after
treatment. "Conclusions Intensive periodontal treatment resulted in
acute, short-term systemic inflammation and endothelial dysfunction.
However, 6 months after therapy, the benefits in oral health were
associated with improvement in endothelial function."
Correlation between atherosclerosis and periodontal putative
pathogenic bacterial infections in coronary and internal mammary
arteries. A Pucar, J Milasin, V Lekovic, M Vukadinovic, M Ristic, S
Putnik, EB Kenney. J Periodontol 2007 Apr;78(4):677-682. By PCR in 15
coronary arteries with atherosclerosis and 15 internal mammary arteries
without, each from the same patient, "Bacterial DNA was found in nine
of 15 (60%) coronary artery biopsy samples: P. gingivalis in eight
(53.33%), A. actinomycetemcomitans in four (26.67%), P. intermedia in
five (33.33%), and T. forsythensis in two (13.33%) samples; CMV was
detected in 10 (66.67%) samples, and C. pneumoniae was detected in five
(33.33%) samples. Some of the samples contained more than one type of
bacteria. Periodontal pathogens were not detected in internal mammary
artery biopsies, whereas CMV was present in seven (46.67%) samples and
C. pneumoniae was present in six (40%) samples. CONCLUSION: The absence
of putative pathogenic bacteria in internal mammary arteries, which are
known to be affected rarely by atherosclerotic changes, and their
presence in a high percentage of atherosclerotic coronary arteries
support the concept that periodontal organisms are associated with the
development and progression of atherosclerosis."
[Detection of periodontal pathogens in coronary
plaques]. LJ Zhong, YM Zhang, H Liu, P Liang, AR Murat, S Askar.
Zhonghua Kou Qiang Yi Xue Za Zhi 2008 Jan;43(1):4-7. Subgingival plaque
samples and coronary atherosclerotic plaques from 31 patients with
periodontitis at coronary artery bypass surgery. "In coronary
atherosclerotic plaques samples from the 31 patients, Porphyromonas
gingivalis (Pg, 38.7%), Actinobacillus actinomycetemcomitans (Aa, 0%),
Fusobacterium nucleatum (Fn, 22.6%), Prevotella intermedia (Pi, 12.9%),
Bacteroides forsythus (Bf, 38.7%) were detected. The concordant
presence of the same periodontal bacteria DNA in subgingival plaques
and in coronary atherosclerotic plaques in the same patient was Pg 5
(16.1%), Aa 0 (0%), Pi 2 (6.5%), Fn 4 (12.9%) and Bf 8 (25.8%)."
Periodontal infection is associated with endothelial
healthy subjects and hypertensive patients. Y Higashi, C Goto, D
Jitsuiki, T Umemura, K Nishioka, T Hidaka, H Takemoto, S Nakamura, J
Soga, K Chayama, M Yoshizumi, A Taguchi. Hypertension 2008
Feb;51(2):446-453. 32 normotensive periodontal patients, 20
normotensive controls, 28 male and 10 female hypertensive patients with
periodontitis, 18 male and 6 female hypertensives without
periodontitis. "Circulating levels of C-reactive protein and
interleukin-6 were significantly higher in the periodontitis group than
in the control group. Both in healthy and hypertensive subjects,
forearm blood flow responses to acetylcholine were significantly
smaller in the periodontitis group than in the control group. Sodium
nitroprusside-stimulated vasodilation was similar in the 2 groups.
Periodontal therapy reduced serum concentrations of C-reactive protein
and interleukin-6 and augmented acetylcholine-induced vasodilation in
periodontitis patients with and without hypertension."
Antibodies to periodontal pathogens and coronary artery
calcification in type 1 diabetic and nondiabetic subjects. HM Colhoun,
JM Slaney, MB Rubens, JH Fuller, A Sheiham, MA Curtis. J Periodontal
Res 2008 Feb;43(1):103-110. 199 type 1 diabetics and 201 nondiabetics.
"Elevated antibody levels were associated with higher systolic blood
pressure (p = 0.02) and an increased odds of coronary artery
calcification in all subjects combined (odds ratio = 1.7, p = 0.047)
and in diabetic subjects examined separately (odds ratio = 2.01, p =
Detection of oral bacteria in cardiovascular specimens. K
Nemoto, R Nomura, H Inaba, H Yoshioka, K Taniguchi, A Amano, T Ooshima.
Oral Microbiol Immunol 2009 Feb;24(1):64-68. Specimens from 203
consecutive patients (82 aortic valve, 35 mitral valve, and 86 aortic
aneurysmal wall specimens). "Streptococcus mutans was the most
frequently detected species in the cardiovascular specimens, followed
by Aggregatibacter actinomycetemcomitans. As for dental plaque
specimens from patients who underwent cardiovascular operations, most
of the tested periodontitis-related species as well as oral
streptococci were detected at high frequencies. Furthermore, the
positive rate of S. mutans in cardiovascular specimens from patients
whose dental plaque specimens were also positive for S. mutans was 78%,
which was significantly higher than any other tested species when the
same analysis was performed."
The collagen-binding protein Cnm is required for Streptococcus mutans adherence to and intracellular invasion of human coronary artery endothelial cells. J Abranches, JH Miller, AR Martinez, PJ Simpson-Haidaris, RA Burne, JA Lemos. Infect Immun 2011 Jun;79(6):2277-2284. "In this study, we demonstrate that in addition to OMZ175 and B14, three other strains (NCTC11060, LM7, and OM50E) of the less prevalent serotypes e and f are able to invade primary human coronary artery endothelial cells (HCAEC). Invasive strains were also significantly more virulent than noninvasive strains in the Galleria mellonella (greater wax worm) model of systemic disease. Interestingly, the invasive strains carried an additional gene, cnm, which was previously shown to bind to collagen and laminin in vitro."Abranches - Infect Immun 2011 full article / PubMed Central
The atherogenic bacterium Porphyromonas gingivalis evades
circulating phagocytes by adhering to erythrocytes. D Belstrøm,
P Holmstrup, C Damgaard, TS Borch, MO Skjødt, K Bendtzen, CH
Nielsen. Infect Immun 2011 Apr;79(4):1559-1565. P. gingivalis fixed
complement component 3 and adhered to red blood cells, which reduced
attack by neutrophils and B cells.
Porphyromonas gingivalis strain specific interactions with human coronary artery endothelial cells: a comparative study. PH Rodrigues, L Reyes, AS Chadda, M Bélanger, SM Wallet, D Akin, W Dunn Jr, A Progulske-Fox. PLoS One 2012;7(12):e52606. "W83 and 381 displayed an equivalent ability to adhere to HCAE cells, which was significantly greater than both A7436 and 33277 (P<0.01). W83, 381, and 33277 were more invasive than A7436 (P<0.0001). However, only W83 and A7436 were able to remain viable up to 48 hours in HCAE cell cultures, whereas 381 was cleared by 48 hours and 33277 was cleared by 24 hours. These differences in persistence were in part due to strain specific differences in intracellular trafficking. Both W83 and 381 trafficked through the autophagic pathway, but not A7436 or 33277. Internalized 381 was the only strain that was dependent upon the autophagic pathway for its survival... Only moderate inflammation was observed in cells infected with either W83 or A7436, whereas cells infected with 381 exhibited the most profound inflammation, followed by cells infected with 33277."Rodrigues - PLoS One 2012 full article / PubMed Central
Bacterial Signatures in Thrombus Aspirates of Patients with Myocardial Infarction. T Pessi, V Karhunen, PP Karjalainen, A Ylitalo, JK Airaksinen, M Niemi, M Pietila, K Lounatmaa, T Haapaniemi, T Lehtimäki, R Laaksonen, PJ Karhunen, J Mikkelsson. Circulation 2013 Mar 19;127(11):1219-1228. 101 male heart patients. "Bacterial DNA typical for endodontic infection, mainly oral viridans streptococci, was measured in 78.2% of thrombi and periodontal pathogens in 34.7%. Bacteria-like structures were detected by transmission electron microscopy in all 9/9 thrombi samples analyzed and whole bacteria in 3/9 cases. Monocyte/macrophage markers for bacteria recognition (CD14) and inflammation (CD68) were detected in thrombi (8/8) by immunohistochemistry. Among the subgroup of 30 MI patients examined by panoramic tomography, a significant association between the presence of periapical abscesses and oral viridans streptococci DNA positive thrombi was found (OR 13.2, 95% CI 2.11 - 82.5; p=0.004)."Pessi - Circulation 2013 abstract / PubMed
Subgingival Aggregatibacter actinomycetemcomitans associates with the risk of coronary artery disease. P Mäntylä, K Buhlin, S Paju, GR Persson, MS Nieminen, J Sinisalo, PJ Pussinen. J Clin Periodontol 2013 Jun;40(6):583-590. 171 patients with stable coronary artery disease, 158 with acute coronary syndrome, 116 with no significant CAD. "With a threshold level of bacterial cells 1 × 10(5) A. actinomycetemcomitans was significantly more prevalent in the Stable CAD group (42.1%) compared to the No CAD group (30.2%) (p = 0.040). In a multi-adjusted logistic regression analysis using this threshold, A. actinomycetemcomitans positivity associated with Stable CAD (OR 1.83, 95% CI 1.00-3.35, p = 0.049), but its level or levels of other bacteria did not."Mäntylä - J Clin Periodontol 2013 abstract / PubMed
Porphyromonas gingivalis infection reduces regulatory T cells in infected atherosclerosis patients. J Yang, J Wu, Y Liu, J Huang, Z Lu, L Xie, W Sun, Y Ji. PLoS One 2014 Jan 23;9(1):e86599. 40 atherosclerosis patients with periodontitis, 32 with tooth loss without atherosclerosis, 29 with no atherosclerosis symptoms or periodontitis. "Our results showed that P.gingivalis infection reduced Tregs in atherosclerotic patients compared with non-atherosclerotic patients and health controls. Concentration of TGF-β1, which plays an important role in the development of Tregs, also decreased in P.gingivalis infected patients. Furthermore, type II FimA seems to show higher prevalence than the other five detected types. The population of Tregs further decreased in patients with type II FimA compared with the other types. P.gingivlias FimA genotype II was the dominant type associated with decreased Treg population."Yang - PLoS One 2014 full article / PubMed Central
Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation. C Slocum, SR Coats, N Hua, C Kramer, G Papadopoulos, EO Weinberg, CV Gudino, JA Hamilton, RP Darveau, CA Genco. PLoS Pathog 2014 Jul 10;10(7):e1004215. "P. gingivalis expresses an atypical lipopolysaccharide (LPS) structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4) agonist or antagonist activity, or are non-activating at TLR4... Oral infection of ApoE-/- mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE-/- mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen."Slocum - PLoS Pathog 2014 full article / PubMed Central
Periodontal bacteria in human carotid atherothrombosis as a potential trigger for neutrophil activation. H Rangé, J Labreuche, L Louedec, P Rondeau, C Planesse, U Sebbag, E Bourdon, JB Michel, P Bouchard, O Meilhac. Atherosclerosis 2014 Aug 11;236(2):448-455. 157 carotid samples. "Intraplaque hemorrhage was present in 73/157 carotid samples and was associated with neutrophil activation, reflected by the release of MPO, cell-free DNA and MPO-DNA complexes. LPS levels were also linked to intraplaque hemorrhage but not with the neutrophil activation markers. Seventy-three percent of the carotid samples were positive for periodontal bacterial DNA. Furthermore, hemoglobin levels were associated with the detection of T. forsythia and neutrophil activation/inflammation markers."Rangé - Atherosclerosis 2014 abstract / PubMed
Contribution of the interaction of Streptococcus mutans serotype k strains with fibrinogen to the pathogenicity of infective endocarditis.R Nomura, M Otsugu, S Naka, N Teramoto, A Kojima, Y Muranaka, M Matsumoto-Nakano, T Ooshima, K Nakano. Infect Immun 2014 Dec;82(12):5223-5234. 85 clinical strains of S. mutans. "The Cbm(+)/PA(-) group strains had significantly higher fibrinogen-binding rates than the other groups. Analysis of platelet aggregation revealed that SA31, a Cbm(+)/PA(-) strain, induced an increased level of aggregation in the presence of fibrinogen, while negligible aggregation was induced by the Cbm-defective isogenic mutant SA31CBD."Nomura - Infect Immun 2014 full article / PubMed Central
Presence of Periodontopathic Bacteria DNA in Atheromatous Plaques from Coronary and Carotid Arteries. M Szulc, W Kustrzycki, D Janczak, D Michalowska, D Baczynska, M Radwan-Oczko. Biomed Res Int 2015;2015:825397. [Porphyromonas gingivalis] "Bacterial DNA was found in 21 of 91 (23%) samples taken from vessels and in 47 of 63 (74.6%) samples from periodontal pockets."Szulc - Biomed Res Int 2015 full article / PubMed Central
Gingipains from the periodontal pathogen Porphyromonas gingivalis play a significant role in regulation of Angiopoietin 1 and Angiopoietin 2 in human aortic smooth muscle cells. B Zhang, H Khalaf, A Sirsjö, T Bengtsson. Infect Immun 2015 Nov;83(11):4256-4265. With TNF as positive control. "We found that P. gingivalis (wild type, K1A, DPG3 and KRX178) and TNF up-regulated the expression of Angpt2 and its transcription factor ETS1, respectively, in AoSMCs. In contrast, Angpt1 was inhibited by P. gingivalis and TNF. However, the RgpA/B mutant E8 had no effect on the expression of Angpt1, Angpt2, or ETS1 in AoSMCs. The results also showed that ETS1 is critical for P. gingivalis induction of Angpt2. Exposure to Angpt2 protein enhanced the migration of AoSMCs but had no effect on proliferation."Zhang - Infect Immun 2015 abstract / PubMed
Molecular Analysis of Oral Bacteria in Heart Valve of Patients With Cardiovascular Disease by Real-Time Polymerase Chain Reaction.FA Oliveira, CP Forte, PG Silva, CB Lopes, RC Montenegro, ÂK Santos, CR Sobrinho, MR Mota, FB Sousa, AP Alves. Medicine (Baltimore) 2015 Nov;94(47):e2067. 42 patients with heart valve disease. "The micro-organism most frequently detected in heart valve samples was the S. mutans (89.3%), followed by P. intermedia (19.1%), P. gingivalis (4.2%), and T. denticola (2.1%). The mean decayed, missing, filled teeth (DMFT) was 26.4 ± 6.9 (mean ± SD), and according to the highest score of periodontal disease observed for each patient, periodontal pockets > 4 mm and dental calculus were detected in 43.4% and 34.7% of patients, respectively."Oliveira - Medicine (Baltimore) 2015 abstract / PubMed
Invasive Streptococcus mutans induces inflammatory cytokine production in human aortic endothelial cells via regulation of intracellular TLR2 and NOD2. E Nagata, T Oho. Mol Oral Microbiol 2016 Mar 23 [Epub ahead of print]. "Five of six strains of S. mutans of various serotypes induced interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 production by HAECs. All S. mutans strains upregulated TLR2 and NOD2 mRNA levels in HAECs. S. mutans Xc upregulated the intracellular TLR2 and NOD2 protein levels in HAECs. Silencing of the TLR2 and NOD2 genes in HAECs invaded by S. mutans Xc led to a reduction in interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 production."Nagata - Mol Oral Microbiol 2016 abstract / PubMed