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Study On Gamma-glutamyltransferase Promote Atherosclerosis Progression

Posted on:2014-10-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:G LiFull Text:PDF
GTID:1224330425973313Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Part I Serum Gamma-glutamyltransferase Levels Can Predict the Progression of Coronary Artery Calcification in Adults with Type2DiabetesObjectives:To determine whether serum gamma-glutamyltransferase (GGT) levels can independtly predict the progression of coronary artery calcification (CAC) in adults with type2diabetes.Methods:A total of326type2diabetic patients free of symptoms of cardiovascular disease were evaluated by CAC imaging. Risk factors, and GGT levels were measured. CAC scores were assessed by a320-slice CT scanner at baseline, followed by20±4months of follow-up. CAC progressors were defined as participants whose square-root transformed CAC volume increased by>2.5mm3Results:A total of172patients (52.8%) showed varying degrees of CAC. GGT levels were higher in progressors than in non-progressors (39±15.6U/L vs.27±10.8U/L, p<0.001). In multivariable analyses, GGT retained a strong association with CAC progression after adjustment for age, gender, and other risk factors (OR [age-and gender-adjusted]1.086[95%CI1.058to1.114], P<0.01; OR [multivariate adjustment]1.082[95%CI1.051to1.114], P<0.01). There also was a graded association between GGT quartile and annualized CAC progression. Among those participants with CAC progression, GGT could predict the increase of CAC scores. Baseline CAC scores and HbAlc were significant predictors of time to cardiovascular events, as indicated by multivariate Cox proportional hazards model.Conclusions:In asymptomatic patients with type2diabetes, we confirm that GGT has a positive correlation with baseline CAC and that serum GGT levels may be an independent predictor of CAC progression but not predictor of CAC incidence. Part II Effects of Atorvastatin Inhibit GGT Expression in the Rabbit Aortic Atherosclerotic PlaquesObjectives:To determine statins affect the GGT expression in the rabbit aortic atherosclerotic plaques and meanwhile to investigate its activity reduced whether make the plaques further stable. The relationship of GGT and other inflammatory factors also be confirmed.Methods:We randomly divided15New Zealand rabbits into three groups:control group, high-cholesterol group and atorvastatin group. To establish the Rabbit Aortic Atherosclerotic model, we fed high-cholesterol food to the high-cholesterol group and atorvastatin group. After the Rabbit Aortic Atherosclerotic model were successfully established, atorvastatin1.5mg·kg-1·d-1continuous feeding statin intervention group of six weeks. We detected rabbit’s plasma TC, TG,LDL,HDL,CRP at0weeks, lOweeks and the end of16weeks. The serum GGT levels were measured at0weeks and the end of16weeks by Using ELISA methods. The expressions of GGT and VCAM in aorta were measured by real-time reverse-transcription PCR and western blot.Result:After10weeks, the plasma LDL, TC levels of high-cholesterol group and atorvastatin group was significantly higher than the control group. The atorvastatin group’s LDL and TG levels were significantly decrease compared with the high-cholesterol group after statins cured. CRP levels were significant difference between each groups. The high-cholesterol group and atorvastatin group’s serum GGT and VCAM levels were significantly increase compared with the control group. Conclusions:Serum GGT levels in the rabbit aortic atherosclerotic model were significant increased. After atorvastatin intervention, the expression of GGT in the local aorta atheromatous plaques was obviously reduced. GGT may be able to promote the development of atherosclerotic plaques. Atorvastatin can effectively inhibit GGT expression in the plaques. This may be a new mechanism of statins anti atherosclerosis.
Keywords/Search Tags:diabetes, coronary artery calcification, gamma-glutamyltransferase, computedtomography, progressionatorvastatin, atherosclerosis, inflammation
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