Helicobacter pylori increases the risk of carotid plaque formation: a clinical evidence.

Background and aim: Since the relation between Helicobacter pylori (H. pylori) and atherosclerosis has been evidenced, we aimed to analyze whether there is a relationship between the patient's H. pylori infection and age, gender, BMI, blood lipids, and carotid plaque formation.Methods: 810 patients from January 2016 to December 2019 were enrolled in this study, and divided the subjects into H. pylori (+) group and H. pylori (-) group based on the results of UBT. To analyze whether H. pylori infection is related to gender, age, BMI, blood lipids, and neck vascular plaque formation.Results: The single-factor analysis showed that the BMI ≥ 25kg/m2, triglycerides >1.7 mmol/l, the formation of cervical plaques were significantly higher in patients infected with H. pylori in compared to normal cases. Also, multi-variant logistic regression analysis showed that H. pylori infection affects the BMI ≥ 25kg/m2 and triglycerides >1.7 mmol/l to induce vascular plaque. Also, we showed that patients with H. pylori infection are 1.424 times higher than the non-infected group to have triglycerides more elevated than 1.7mmol/l.Conclusion: In this study, we conclude that H. pylori infection is an independent risk factor for higher BMI (>25), triglyceride (>1.7 mmol/l), and neck vascular plaque formation. The multi-variant analysis showed that patients with H. pylori infection are prone to have higher BMI, triglycerides, and neck vascular plaque formation over 1.4-times higher in non-infected individuals.KEY MESSAGESH. pylori infection is an independent risk factor for higher BMI, triglyceride, and neck vascular plaque formation.H. pylori can accelerate vascular plaque formation through increasing BMI and triglyceride.

Bacterial invasion of vascular cell types: vascular infectology and atherogenesis.

To portray the chronic inflammation in atherosclerosis, leukocytic cell types involved in the immune response to invading pathogens are often the focus. However, atherogenesis is a complex pathological deterioration of the arterial walls, where vascular cell types are participants with regards to deterioration and disease. Since other recent reviews have detailed the role of both the innate and adaptive immune response in atherosclerosis, herein we will summarize the latest developments regarding the association of bacteria with vascular cell types: infections as a risk factor for atherosclerosis; bacterial invasion of vascular cell types; the atherogenic sequelae of bacterial presence such as endothelial activation and blood clotting; and the identification of the species that are able to colonize this niche. The evidence of a polybacterial infectious component of the atheromatous lesions opens the doors for exploration of the new field of vascular infectology and for the study of atherosclerosis microbiome.

Chlamydia pneumoniae induces chemokine expression by platelets in patients with atherosclerosis.

OBJECTIVE: In this study, the role of Chlamydia pneumoniae in triggering platelets to induce the inflammatory potential chemokines CCL3, CCL5, CCL7 and CXCL8 in atherosclerotic patients was investigated. SUBJECTS AND METHODS: Venous blood from control subjects (n = 35) and atherosclerotic patients (n = 35) was collected in tubes with and without EDTA. Platelets from controls and patients were separated from whole blood and then stimulated with lipopolysaccharide (LPS), live C. pneumoniae and heat-treated C. pneumoniae. The ability of C. pneumoniae and its LPS to stimulate platelets and expression of CCL3, CCL5, CCL7 and CXCL8 was assessed with immunofluorescence. Immunosorbent assays were used to detect anti-C. pneumoniae antibodies in sera from patients and healthy subjects. RESULTS: Nonstimulated platelets from patients showed significant expression of CCL3, CCL5, CCL7 and CXCL8 compared to controls (p < 0.0001). Stimulation of platelets from patients with live and heat-treated C. pneumoniae and its LPS demonstrated significant induction of chemokines compared to similarly stimulated platelets from controls (p < 0.01). After stimulation with heat-treated C. pneumoniae chemokine expression in platelets from controls was significantly lower than after stimulation with live C. pneumoniae (p < 0.01), which was not the case when platelets from patients were stimulated. Increased levels of anti-C. pneumoniae antibodies were detected in sera from patients compared to healthy subjects, suggesting prior C. pneumoniae exposure. CONCLUSION: Our data demonstrated an interactive link between C. pneumoniae and platelets in atherosclerotic patients, leading to induction of potential chemokines and possibly disease development.

[Helicobacter pylori and Arteriosclerosis].

Helicobacter pylori (H. pylori) infection-related diseases are known to include gastritis, gastric and duodenal ulcer, gastric cancer, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, iron-deficient anemia, urticaria, reflux esophagitis, and some lifestyle-related diseases. It is indicated that homocysteine involved with arteriosclerosis induces lifestyle-related diseases. Homocysteine is decomposed to methionine and cysteine (useful substances) in the liver, through the involvement of vitamin B12 (VB12) and folic acid. However, deficiency of VB12 and folic acid induces an increase in unmetabolized homocysteine stimulating active oxygen and promoting arteriosclerosis. VB12 and folic acid are activated by the intrinsic factors of gastric parietal cells and gastric acid. The question of whether homocysteine, as a trigger of arteriosclerosis, was influenced by H. pylori infection was investigated. H. pylori infection induces atrophy of the gastric mucosa, and the function of parietal cells decreases with the atrophy to inactivate its intrinsic factor. The inactivation of the intrinsic factor causes a deficiency of VB12 and folic acid to increase homocysteine's chances of triggering arteriosclerosis. The significance and usefulness of H. pylori eradication therapy was evaluated for its ability to prevent arteriosclerosis that induces lifestyle-related diseases. Persons with positive and negative results of H. pylori infection were divided into a group of those aged 65 years or more (early and late elderly) and a group of those under 65 years of age, and assessed for gastric juice. For twenty-five persons from each group who underwent gastrointestinal endoscopy, the degree of atrophy of the gastric mucosa was observed. Blood homocysteine was measured as a novel index of arteriosclerosis, as well as VB12 and folic acid that affect the metabolism of homocysteine, and then activated by gastric acid and intrinsic factors. Their arterioscleroses, measured by pulse wave velocity (PWV), were investigated and compared. The levels of homocysteine were significantly high in the elderly persons and those with H. pylori infection. On the contrary, the levels of VB12 and folic acid were low in these persons. The results of PWV showed a positive correlation with the levels of gastrin and homocysteine and an inverse correlation with the levels of VB12 and folic acid. Persons with a negative result of H. pylori infection showed a lower degree of arteriosclerosis than those with a positive result who were of the same age group. Persons with a positive result of H. pylori infection tended to show an improvement from arteriosclerosis after eradication therapy without a significant difference. 1 ) It is suggested that severity of atrophy of the gastric mucosa are correlated with the severity of arteriosclerosis. 2 ) It is hypothesized that H. pylori infection may induce arteriosclerosis.

[Chlamydophila pneumoniae: from its proteomics to arteriosclerosis]. / Chlamydophila pneumoniae: desde su proteómica hasta la arteriosclerosis.

Chlamydophila pneumoniae is a highly prevalent intracellular human pathogen with a unique biphasic life cycle. It is a common cause of upper respiratory infection and pneumonia, and is currently being studied as a potential risk factor for the development of atherosclerotic cardiovascular disease. The outer membrane surface antigens of C. pneumoniae are highly complex: some, such as the major outer membrane protein, are specific, but poorly immunodominant, whereas others have stronger immunogenicity, but are cross-reactive among Chlamydia species. Therefore, new, highly immunodominant, species-specific antigens should be sought. In this regard, the polymorphic membrane proteins (PMPs) are a) unique to Chlamydiae, b) often exposed on the surface of the bacteria, and c) highly immunogenic; these factors make them potential candidates for application in laboratory assays. Other chlamydial antigens, such as heat shock protein (HSP) 60, have been associated with atherosclerotic lesions because of their ability to induce an immunological attack on the endothelial wall. Over the last decade, several studies have suggested a potential role of chronic C. pneumoniae infection in human atherosclerosis. Nevertheless, prospective studies with sufficiently large samples and a healthy comparison group, using a combination of direct and indirect microbiological techniques in the same subject and sample, are needed to establish a relationship between the infection and disease activity.

Chlamydophila pneumoniae: desde su proteómica hasta la arteriosclerosis / Chlamydophila pneumoniae: from proteomics to arteriosclerosis

Chlamydophila pneumoniae es un patógeno humano intracelular, muy prevalente, con un ciclo único de desarrollo bifásico, que causa infecciones respiratorias en las vías altas y neumonía, y que actualmente se cree que puede ser un factor de riesgo para el desarrollo de la arteriosclerosis.C. pneumoniae muestra una gran complejidad en los antígenos de superficie de la membrana externa, ya sea por ser específicos pero poco inmunógenos (como la proteína principal de la membrana externa) o bien por ser muy inmunógenos pero poco específicos entre las especies de clamidias. Todo esto hace necesario profundizar en el estudio de nuevos antígenos que sean altamente inmunodominantes y específicos de especie. En este sentido, las proteínas polimórficas de la membrana externa (PMP) son a) específicas de clamidia, b) se exponen en la superficie de la bacteria y c) son muy inmunógenas, todo lo cual las hace acreedoras de un importante potencial de aplicación en los diferentes ensayos de laboratorio. Otras, como la proteína de choque térmico 60 (HSP 60), parecen estar relacionadas con la arteriosclerosis, por inducir un ataque inmunológico sobre la pared endotelial. A partir de los estudios existentes hasta la fecha, para obtener una conclusión sobre la relación entre la infección y la arteriosclerosis, faltan estudios con suficiente número de pacientes y muestras, prospectivo, comparativo frente a controles sanos, que utilicen la combinación de varias técnicas microbiológicas (directas e indirectas) en un mismo sujeto y muestra, relacionando los resultados con la actividad de la enfermedad (AU)

Chlamydophila pneumoniae is a highly prevalent intracellular human pathogen with a unique biphasic lifecycle. It is a common cause of upper respiratory infection and pneumonia, and is currently being studied as a potential risk factor for the development of atherosclerotic cardiovascular disease. The outer membrane surface antigens of C. pneumonia are highly complex: some, such as the major outer membrane protein, are specific, but poorly immunodominant, whereas others have stronger immunogenicity, but are cross-reactive among Chlamydia species. Therefore, new, highly immunodominant, species-specific antigens should be sought. In this regard, the polymorphic membrane proteins (PMPs) are a) unique to Chlamydiae, b) often exposed on the surface of the bacteria, and c) highly immunogenic; these factors make them potential candidates for application in laboratory assays. Other chlamydial antigens, such as heat shock protein (HSP) 60, have been associated with atherosclerotic lesions because of their ability to induce an immunological attack on the endothelial wall.Over the last decade, several studies have suggested apotential role of chronic C. pneumoniae infection in human atherosclerosis. Nevertheless, prospective studies with sufficiently large samples and a healthy comparison group, using a combination of direct and indirect microbiological techniques in the same subject and sample, are needed to establish a relationship between the infection and disease activity (AU)

Morphometrical quantification of Chlamydia pneumoniae and Mycoplasma pneumoniae in human atherosclerotic abdominal aortic aneurysms.

OBJECTIVE: Atherosclerotic inflammation with a possible role of infectious agents can contribute to the pathogenesis of abdominal aortic aneurysms (AAA). The finding of Chlamydia pneumoniae (CP) in these lesions in previous non-quantifying studies ranged from 0-100%. The objective is to quantify the presence of CP and Mycoplasma pneumoniae (MP) in AAA. METHODS: The thickness, and the number of cells positive for CP detected by the immunohistochemistry (immunoperoxidase, which is a type of immunohistochemical stain used in molecular biology, medical research, and clinical diagnostics), and the percentage of the area occupied by the Mycoplasma pneumoniae detected by in situ hybridization in three layers of the aorta were measured using an image-analysis system in 10 necropsies of abdominal aneurysmatic aortas. Three groups were used as controls: 1) samples of the same aortas, outside the aneurysms, except if the dilatation took the whole sub-renal portion of the artery (n=7); 2) aortas with severe atherosclerosis but without aneurysms (n=10); 3) aortas without or with mild atherosclerosis (n=10). All specimens were obtained at necropsies. Wald's test was used to compare groups; significance level was established at 5%. RESULTS: The tunica intima was thinner and the tunica media was thicker in the normal cases than in the other groups (p<0.01). Positive cells for CP were found in all groups, more frequently at the adventitia; no significant difference was detected between the groups (p>0.05). MP was also detected in all groups. This agent predominated in the group of patients with atherosclerosis, but without aneurysms at both tunica intima and adventitia; nevertheless, there were no significant differences between the groups (p>0.05). CONCLUSIONS: Our data suggested that the bacteria we focused to, does not play an important role in the pathogenesis of AAA.

[Isolation of periodontal bacteria from blood samples and atheromas in patients with atherosclerosis and periodontitis]. / Aislamiento de bacterias periodontopáticas desde hemocultivos y ateromas obtenidos de pacientes con aterosclerosis y periodontitis.

BACKGROUND: Periodontitis is a common oral disease produced by bacterial species that reside in the subgingival plaque. These microorganisms have been associated to atherosclerosis and it is suggested that periodontitis is a cardiovascular risk factor. AIM: To isolate periodontal bacteria from blood and atheroma samples, from patients with atherosclerosis and periodontitis. MATERIAL AND METHODS: Twelve patients with periodontitis and a clinical diagnosis of atherosclerosis and 12 patients with periodontitis but without atherosclerosis were studied. Blood samples were obtained immediately before and after scaling and root planing. The samples were incubated in aerobic and anaerobic conditions. One week after scaling, atheromatous plaques were obtained during endarterectomy in the 12 patients with atherosclerosis. These were homogenized and cultured for aerobic and anaerobic bacteria. Microorganisms were identified by means ofPCR. RESULTS: Five patients with and two without atherosclerosis, had bacteremia after scaling and root planing. Bacterial species isolated from blood samples were the same found in periodontic pockets. Four atheromatous plaques of patients with bacteremia yielded positive cultures. The isolated bacteria were the same found in blood samples and periodontal pockets. CONCLUSIONS: Bacteremia occurred in seven of 24 patients after scaling and root planing. In four patients, the same species found in periodontic pockets and blood cultures were detected in atherosclerotic plaques obtained one week after the dental procedure.

Aislamiento de bacterias periodontop ticas desde hemocultivos y ateromas obtenidos de pacientes con aterosclerosis y periodontitis / Isolation of periodontal bacteria from blood samples and atheromas in patients with atherosclerosis and periodontitis

Background: Periodontitis is a common oral disease produced by bacterial species that reside in the subgingival plaque. These microorganisms have been associated to atherosclerosis and it is suggested that periodontitis is a cardiovascular risk factor. Aim: To isolate periodontal bacteria from blood and atheroma samples, from patients with atherosclerosis and periodontitis. Material and methods: Twelve patients with periodontitis and a clinical diagnosis of atherosclerosis and 12 patients with periodontitis but without atherosclerosis were studied. Blood samples were obtained immediately before and after scaling and root planing. The samples were incubated in aerobic and anaerobic conditions. One week after scaling, atheromatous plaques were obtained during endarterectomy in the 12 patients with atherosclerosis. These were homogenized and cultured for aerobic and anaerobic bacteria. Microorganisms were identified by means ofPCR. Results: Five patients with and two without atherosclerosis, had bacteremia after scaling and root planing. Bacterial species isolated from blood samples were the same found in periodontic pockets. Four atheromatous plaques of patients with bacteremia yielded positive cultures. The isolated bacteria were the same found in blood samples and periodontal pockets. Conclusions: Bacteremia occurred in seven of 24 patients after scaling and root planing. In four patients, the same species found in periodontic pockets and blood cultures were detected in atherosclerotic plaques obtained one week after the dental procedure.

[Contemporary views on the pathogenesis of atherosclerosis].

Recent studies show that inflammation plays the key role inthe pathogenesis of atherosclerosis. Immune cells dominate at the initial stages of the atherosclerotic lesion of blood vessels. The effector molecules accelerate the progress of the lesion. This approach to the assessment of the pathogenesis of atherosclerosis makes it possible to search the ways for the prevention and suppression of immune inflammation. Nowadays vaccination against primary autoantigens is being successfully used for protection from experimental atherosclerosis. Modulation of immune response, involved in atherosclerosis, includes vaccination inducing immune protecting response of the development of tolerance by means of the process from Th1 to Th2 cell response.

Role of chlamydia infection in the pathogenesis of atherosclerotic plaques in HIV-1-positive patients.

BACKGROUND: Various authors have hypothesized a role of Chlamydia pneumoniae infection in the pathogenesis of atherosclerosis. To better understand the possible role of this infection in the pathogenesis of epi-aortic lesions in HIV-1-positive patients, the presence of anti-Chlamydia pneumoniae antibodies was evaluated in a group of individuals subjected to ultrasonography of the epi-aortic vessels. PATIENTS AND METHODS: The presence of specific antibodies in 129 subjects was determined; 59 patients were HIV-1-positive, of whom 30 had carotid plaques and 29 were without lesions. The control group was composed of 70 subjects. All were subjected to ultrasonography of the epi-aortic vessels. IgG, IgM and IgA anti-C. pneumoniae antibodies were measured with micro-immunofluorescence and positive sera were tested for C. trachomatis and C. psittaci. RESULTS: No subjects were positive for IgM. Both the IgA and IgG levels did not differ significantly in the three groups. The only highly significant variable was the use of protease inhibitors. CONCLUSION: Our data suggest that the damage to the carotid wall in HIV-1 patients was not due to C. pneumoniae.

Estrategia de multidetección de Chlamydia pneumoniae en pacientes con enfermedad arterial periférica: el problema de evaluar la relación entre la infección y la enfermedad / Detectetion of Chlamydia pneumoniae in patients with peripheral arterial occlusive disease: relationship between infection and disease

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Isolation of Chlamydophila pneumoniae from atheromas of the carotid artery and their antibiotics susceptibility profile

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Detection of nanobacteria-like particles in human atherosclerotic plaques.

Recent and historical evidence is consistent with the view that atherosclerosis is an infectious disease or microbial toxicosis impacted by genetics and behavior. Because small bacterial-like particles, also known as nanobacteria have been detected in kidney stones, kidney and liver cyst fluids, and can form a calcium apatite coat we posited that this agent is present in calcified human atherosclerotic plaques. Carotid and aortic atherosclerotic plaques and blood samples collected at autopsy were examined for nanobacteria-like structures by light microscopy (hematoxylin-eosin and a calcium-specific von Kossa staining), immuno-gold labeling for transmission electron microscopy (TEM) for specific nanobacterial antigens, and propagation from homogenized, filtered specimens in culture medium. Nanobacterial antigens were identified in situ by immuno-TEM in 9 of 14 plaque specimens, but none of the normal carotid or aortic tissue (5 specimens). Nanobacteria-like particles were propagated from 26 of 42 sclerotic aorta and carotid samples and were confirmed by dot immunoblot, light microscopy and TEM. [3H]L-aspartic acid was incorporated into high molecular weight compounds of demineralized particles. PCR amplification of 16S rDNA sequences from the particles was unsuccessful by traditional protocols. Identification of nanobacteria-like particles at the lesion supports, but does not by itself prove the hypothesis that these agents contribute to the pathogenesis of atherosclerosis, especially vascular calcifications.

Effects of repeated Chlamydia pneumoniae inoculations on aortic lipid accumulation and inflammatory response in C57BL/6J mice.

Chlamydia pneumoniae is a common respiratory tract pathogen, and persistent infections have been associated with atherosclerosis. We studied the effects of repeated chlamydial inoculations on the inflammatory response and on aortic lipid accumulation in C57BL/6J mice. Mice fed a diet supplemented with 0.2% cholesterol were infected three or six times with C. pneumoniae every fourth week. Sera and lungs were analyzed for inflammatory responses, lung tissues were tested for the presence of C. pneumoniae DNA and RNA, and intimal lipid accumulation in the aortic sinus was quantified. High levels of chlamydial heat shock protein 60 (Hsp60) immunoglobulin G2c subclass antibodies were detected in all of the infected mice, and a positive and statistically significant correlation was found between these antibodies and autoantibodies against mouse Hsp60. Both Hsp60 antibody levels correlated with the severity of lung tissue inflammation. The cholesterol supplement in the diet had no effect on serum cholesterol levels. Significantly larger intimal lipid lesions were seen in the mouse group infected six times (6,542 mum(2)) than in the control group (1,376 mum(2); P = 0.034). In conclusion, repeated inoculations increased aortic sinus lipid accumulation in normocholesterolemic mice. The correlation between the antibodies to mouse and chlamydial Hsp60 proteins and their association with lung inflammation further support the theory of the development of an autoimmune response against heat shock proteins after repeated chlamydial infections.