Association Between H.Pylori Infection And Atherosclerosis

PartⅠPrevalence of H.pylori infection in acute coronary syndrome patients and the investigation of the association between H.pylori infection and acute coronary syndrome.Objective: To investigate the possible association between acute coronary syndrome (ACS) and infection with H.pylori and its virulent strains. To evaluate the effects of H.pylori infection on the serum levels of lipid concentrations and inflammatory parameters such as CRP, fibrinogen, leukocyte count and platelet count . Methods: H.pylori IgG antibodies were assessed by ELISA in 358 patients with ACS and 327 controls. CagA and VacA proteins were tested by Western-blot assay in patients with H.pylori seropositivity. Measured plasma inflammatory parameters and lipid concentrations. Results: (1)Prevalence of H.pylori IgG was higher in ACS patients than in controls (57.8% vs 44.3%, P<0.05), the H.pylori seropositivity was associated with ACS, OR=1.72(95%CI 1.27~2.33), after adjustment for age, gender, smoking, hypertension, hyperlipidemia and diabetes, the association was still seen, OR=1.48(95%CI 1.09~2.00). (2)ACS patients also had a higher prevalence of CagA and VacA positive H.pylori strains(40.5% vs 23.5%), and adjusted odds ratio of 2.02(95%CI 1.43~2.87), P<0.05. (3)Inflammatory parameters and lipids concentrations were significantly higher in H.pylori positive subjects than in H.pylori negative subjects. Conclusion: H.pylori seropositivity is an independent risk factor for ACS, infection with CagA and VacA positive strains appear to be more related to the disease than other strains. The increased systemic inflammatory parameters and lipids concentration in ACS patients seem to be related to H.pylori seropositivity.PartⅡDetection of H.pylori DNA in atherosclerotic plaques and its association with H.pylori infectionObjective: To investigate the presence of H.pylori DNA in atherosclerotic plaques by PCR and to evaluate the correlation between the DNA positivity and the development of atherosclerosis. Methods: H.pylori IgG antibodies were assessed by ELISA in 32 patients before autopsies. CagA and VacA proteins were tested by Western-blot assay in 20 patients with H.pylori seropositivity and plasma CRP levels and lipid profiles were measured. In patients with H.pylori IgG antibody seropositivity, ureC, cagA and vacA gene were tested by PCR in the arteries. Results: (1) The H.pylori seropositivity was associated with incidence of atherosclerosis, OR=7.00(95%CI 1.39~35.36). (2)Infection with CagA and VacA positive H.pylori strains significantly increased the incidence of atherosclerosis, OR=33.0(95%CI 2.91~374.5). (3) ureC DNA were founded in 4 of 14 samples of atherosclerotic plaques, whereas none of the controls revealed positive DNA. cagA and vacA gene were not founded in all atheroscerotic plaques and normal arteries. (4) C-reactive proein (CRP) and lipid profile were significantly different between H.pylori seropositive group and seronegative group. Conclusion: H.pylori infection especially CagA and VacA positive strains infection is a risk factor for atherosclerosis.The presence of H.pylori DNA in number of atherosclerotic plaques but their absence in healthy vascular wall supports the idea that H.pylori infection may have a role in the development of atheroslcerosis. The seropositivity of H.pylori could affect the levels of inflammatory parameters and lipid profile.PartⅢEstablishment of H. pylori infected C57BL/6 mice model and the role of H. pylori infection in atherosclerosis progression.Objective: To investigate the effect of chronic H. pylori infection on the development and progression of atherosclerosis in C57BL/6 mice. Method: 48 female C57BL/6 mice which were 8 weeks old were randomly divided into 4 groups: infected with H. pylori and fed a high-cholesterol diet, without H. pylori infection and fed a high-cholesterol diet, infected with H. pylori and fed a normal chow diet and control. After 52 weeks plasma levels of lipids were measured. The aortic atherosclerotic lesions formation and lipid deposition was evaluated by histology to compare the extent of atherosclerosis between the 4 groups. The ureC, cagA and vacA DNA were detected by PCR in the aortic ateries of mice. Result: (1) H.pylori infected mice showed more obvious inflammation in gastric mucosa than H.pylori uninfected mice. (2)Either in the groups fed with a chow diet or a high-cholesterol diet, the plasma levels of triglyceride, total cholesterol and low density lipoprotein (LDL) were higher and high density lipoprotein (HDL) were lower in mice infected with H. pylori than without H. pylori. (3)Aortic atheroscl erotic plaque was not observed in mice fed with a chow diet. However, significant plaque formation were observed in mice fed with a high-cholesterol diet, moreover, the atherosclerotic lesion area was significantly higher in mice infected with H.pylori infection than without H.pylori infection. (4) 5 of 12 ureC DNA were detected in aortic arteries of mice infected with H. pylori and fed a high-cholesterol diet, none of cagA and vacA DNA were found in all specimen. Conclusion: This study demonstrated that chronic H. pylori infection might influence the plasma levels of lipids and contribute to the development of atherosclerotic lesion formation in the mouse model of atherosclerosis with hyperlipidemia. Existence of ureC DNA in atherosclerosis plaques show that pathogen may be a cause of atherosclerosis.PartⅣAnalysis of immune response in mice with atherosclerosis and H. pylori infection. Objective: To investigate the effect of immune response induced by H. pylori infection on the progression of atherosclerosis in C57BL/6 mice. Method: 48 female 8 weeks old C57BL/6 mice were randomly divided into 4 groups: infected with H. pylori and fed a high-cholesterol diet, without H. pylori infection and fed a high-cholesterol diet, infected with H. pylori and fed a normal chow diet and wild type C57BL/6 mice as control. We assesed the T lymphocytes proliferative response and the changes of T lymphocyte subpopulatins between the four groups. Measured the levels of IL-1β, TNF-αand IL-6 in supernatant of mice peritoneal macrophage culture by ELISA. Results: (1) Proliferative responses took place in the all four groups, there were a link between the H.pylori antigen concentration and the proliferative response. Either in mice fed with high-cholesterol diet or normal chow diet, the infected mice showed increased proliferative responses compared with the uninfected mice. (2) Increased Th1 type T cell response were seen in the infected mice and high-cholesterol diet fed mice, the infected mice fed with high-cholesterol diet exhibited the highest Th1 type T cell response in the four groups. (3) IL-1β, TNF-αand IL-6 were higher in H.pylori infected groups and hyperlipidemic groups. Conclusion: H.pylori infection could cause T lymphocytes proliferative response in normal and atherosclerosis mice. Increased Th1 type T cell response and secretion of cytokines induced by peritoneal macrophages have association with H.pylori infection and atherosclerosis...