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Meta - Analysis Of Diet And Cardiovascular Risk And Experimental Study On Anti - Inflammatory Mechanism Of Green Tea Polyphenol EGCG

Posted on:2015-08-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z M WangFull Text:PDF
GTID:1104330467960116Subject:Internal Medicine
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Part I. Dietary intake and risk of cardiovascular disease: a meta-analysisObjective:Cardiovascular disease (CVD) is still the most common cause of death worldwide. Dietary factors are now considered to play an important role in the prevention of CVD. Epidemiologic studies are inconsistent regarding the association between diet and CVD risk. The objective was to perform a meta-analysis to determine whether an association exists between tea consumption and dietary intake of nutrients (folate, flavonols and magnesium) and the risk of CVD.Methods:We searched the PubMed and EMBASE databases for studies conducted from1966through2013. Epidemiologic studies that provided risk estimates with95%confidence intervals (CIs) for the association were included. Data were independently abstracted by two investigators using a standardized protocol. Study-specific risk estimates were combined by using a random effects model.Results:A total of44studies were included in the meta-analysis. For the association between black tea consumption and CHD risk (n=13), the summary relative risk (RR) did not indicate a significant association (highest compared with lowest, summary RR:0.92;95%CI:0.82,1.04; an increment of one cup/day, summary RR:0.98;95%CI:0.94,1.02); for the association between green tea consumption and CHD risk (n=5), the summary RR indicated a significant inverse association (highest compared with lowest, summary RR:0.72;95%CI:0.58,0.89; an increment of one cup/day, summary RR:0.90;95%CI:0.82,0.99); for the association between dietary folate intake and CHD risk (n=7), the summary RR indicated a significant inverse association (highest compared with lowest, summary RR:0.69;95%CI:0.60,0.80; an increment of200μg/day, summary RR:0.88;95%CI:0.82,0.94); for the association between dietary flavonols intake and CHD risk (n=9), the summary RR did not indicate a significant association (highest compared with lowest, summary RR:0.91;95%CI:0.83,1.01; an increment of20mg/day, summary RR:0.96;95%CI:0.90,1.03); for the association between dietary flavonols intake and stroke risk (n=8), the summary RR indicate a significant inverse association (highest compared with lowest, summary RR:0.86;95%CI:0.75,0.99; an increment of20mg/day, summary RR:0.86;95%CI:0.77,0.96); for the association between dietary magnesium intake and stroke risk (n=8), the summary RR indicate a significant inverse association (highest compared with lowest, summary RR:0.89;95%CI:0.82,0.97; an increment of100mg/day, summary RR:0.98;95%CI:0.95,1.00).Conclusions:This meta-analysis suggests that green tea consumption and dietary folate intake are associated with a significant reduced risk of CHD, whereas black tea consumption and dietary flavonols intake are not inversely associated with CHD risk. Higher dietary intake of flavonols and magnisium are associated with a reduced risk of stroke.Part Ⅱ. The anti-inflammatory effects of green tea polyphenol EGCG in HUVECsObjective:Epidemiological studies and associated meta-analyses have reported that daily consumption of green tea is associated with a reduced risk of CVD. Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, displays a variety of pharmacological properties and recently received attention as a prospective dietary intervention in CVD. This study was conducted to test the hypothesis that EGCG was able to inhibit tumor necrosis factor-a (TNF-a)-induced production of monocyte chemoattractant protein-1(MCP-1) in human umbilical vein endothelial cells (HUVECs) and investigated the underlying molecular mechanisms.Methods:The inhibitory effect of EGCG on TNF-a-induced expression of MCP-1was measured using ELISA and RT-qPCR. The effect of EGCG on TNF-a-induced nuclear factor-kappa B (NF-κB) activation was investigated by western blot and luciferase assays. Monocyte adhesion assay was detected by microscope.Results:EGCG significantly suppressed the TNF-a-induced protein and mRNA expression of MCP-1. Investigation of the mechanism suggested that EGCG suppressed the TNF-a-mediated NF-κB activation. In addition, the67-kD laminin receptor (67LR) was involved in EGCG-mediated suppression of MCP-1generation. Furthermore, EGCG potently inhibited monocyte adhesion to activated HUVECs.Conclusion:EGCG suppresses TNF-a-induced MCP-1expression in HUVECs. This effect was mediated by67LR and was via the inhibition of NF-κB activation. Our result shows that EGCG plays a protective role against endothelial dysfunction induced by TNF-a; this may be a putative mechanism for the anti-atherosclerotic effects of green tea consumption and may help us to better understand the beneficial effects of green tea consumption proved in our previous meta-analysis.
Keywords/Search Tags:diet, tea, EGCG, cardiovascular disease, meta-analysis
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