Detection of Treponema denticola in Atherosclerotic Lesions

Abstract

We examined 26 atherosclerotic lesions and 14 nondiseased aorta specimens to detect the periodontopathogenic part of the bacterial 16S rRNA locus by PCR. Treponema denticola sequence of the 16S rRNA locus was found in 6 out of 26 DNA samples (23.1%) from the formalin-fixed, paraffin-embeded atherosclerotic lesions obtained during surgery but not in any of the 14 nondiseased aorta samples from deceased persons. Utilizing immunofluorescence microscopy, we observed aggregated antigenic particles reacting with rabbit antiserum against T. denticola in thin sections of the PCR-positive samples, but we could not detect any reacting particles in the PCR-negative thin sections.Recent epidemiological studies have established that rheological and hemostatic factors are related to vascular diseases. These factors are potential biological effectors which may interact with known risk factors such as hyperlipidemia, smoking, and infections to promote vascular events. A number of studies have suggested that infectious organisms may play a role in the etiology and epidemiology of atherosclerosis and related diseases (5,6,9,29). For one such organism, Chlamydia pneumoniae, there is mounting evidence associating infections with a greater risk of atherosclerosis, myocardial infarction, and chronic coronary heart disease (3,20,26). Persistent infections by the obligate intracellular gram-negative bacteria are involved in a wide spectrum of respiratory diseases. It is now recognized that chronic oral infections, such as adult periodontitis, may have important long-term sequelae (2,7,10,16,19,(21)(22)(23)(24)28). An inflammatory response to endothelial cell injury and dysfunction caused by these infections may lead to atherosclerosis (26). Recently, Haraszthey et al. (11) reported that periodontal organisms such as Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Bacteroides forsythus, and Prevotella intermedia were detected in atheromatous plaque by PCR. In the present study, we attempted to detect periodontopathic bacterial DNA in atherosclerotic vascular lesions.To detect A. actinomycetemcomitans, P. gingivalis, B. forsythus, Campylobacter rectus, and Treponema denticola, we used the PCR and followed a double-blind protocol. The primers for detecting part of the bacterial 16S rRNA locus by PCR were synthesized in accordance with previously reported procedures (1, 30). Primer pairs for T. denticola (5Ј-TAATACCG AATGTGCTCATTTACAT-3Ј and 5-TCAAAGAAGCATTC CCTCTTCTTCTTA-3Ј), B. forsythus (5Ј-GCGTATGTAACC TGCCCGCA-3Ј and 5Ј-TGCTTCAGTGTCAGTTATACCT-3Ј), and C. rectus (5Ј-TTTCGGAGCGTAAAACTCCTTTTC-3Ј and 5Ј-TTTCTGCAAGCAGACACTTTT-3Ј) were designed on the basis of 16S rRNA (1). Primer pairs for P. gingivalis (5Ј-ATAATGGAGAACAGCAGGAA-3Ј and 5Ј-TCTTGCC AACCAGTTCCATTGC-3Ј) and A. actinomycetemcomitans (5Ј-CAGCAAGCTGCACAGTTTGCAAA-3Ј and 5Ј-CATTA GTTAATGCCGGGCCGTCT-3Ј) were designed on the basis of fimbriae and leukotoxin (30). Primer pairs for C. pneumoniae (5Ј-TGACAACTGTAGAAATACAGC-3Ј and 5Ј-GG TTGAGRTCAACGACTTAAGG-3Ј) were designe...

Alzheimer's Disease and Peripheral Infections: The Possible Contribution from Periodontal Infections, Model and Hypothesis

“…Metastasizing at distant sites periodontal bacteria are capable of inducing pathology. For example, A. actinomycetemcomitans, P. gingivalis and T. denticola were recovered in atherosclerotic plaques [39,90] and P. Gingivalis induced the expression of adhesion molecules and proinflammatory cytokines in aortic tissue and accelerated atherosclerosis in an animal model (apolipoprotein E-deficient mice) [34]. In another animal model (BALB/C mice), infection with C. rectus induced decreased expression of Insulin Growth Factor 2 (IGF2) mRNA by epigenetic modification of the Igf2 gene [13] and induced placental structural changes.…”

Apolipoprotein E Related Co-Morbidities and Alzheimer’s Disease

“…Since CRP is a predictor of heart disease, its rise during episodes of poor dental hygiene is currently the strongest link between PD and atherosclerotic vascular disease (ASVD). Translocation of oral pathogens into the main arterial vessels is reported by many investigators using sensitive polymerase chain reaction (PCR) and sequencing alongside the fluorescence in-situ hybridisation (FISH) technique [93][94][95][96][97]. These include P. gingivalis and T. denticola located within the walls of human coronary artery and atheromatous plaque lesions [93][94][95][96][97].…”

“…These include Chlamydophila pneumoniae [C. pneumoniae], T. denticola, P. gingivalis which are also found in atheroma plaque tissues [93][94][95][96][97] and in AD brains [56,60,125], herpes simplex virus type I [126], and several species of spirochetes of which the well cited ones are T. denticola [56] and Borrelia burgdorferi [127]. Although the exact aetiological agent(s) responsible the lateonset AD (LOAD) remain elusive, spirochetes appear as highly plausible candidates as exemplified by the condition long-standing, stationary or atrophic form of general paresis, which is caused by Treponema pallidum…”

Periodontopathic Bacteria and Their Potential Involvement in Atherosclerosis

“…Periodontopathic bacteria such as Porphyromonas gingivalls, Actlnobaclllus actinomycetemcomitans, Bacteroldesforsythus, and Treponema denticola have been detected in human atheromas (14,15 It should be pointed out that the leakage of viable organisms into the circulation is not necessary to fulfill a role for periodontopathic bacteria in CD since outer membrane vesicles (OMVs) or lipopolysaccharides (LPS) present in membrane fragments released from these organism exhibit many of the pathogenic properties of the viable organisms (17).…”