| Objective:1. To detect the p66shc mRNA and protein levels in peripheral blood monocytes (PBMs) of patients with acute coronary syndrome (ACS) and controls.2. To compare the endothelium-dependent flow-mediated vasodilation (FMD), endothelium-independent nitroglycerin-induced vasodilatation (NID) and carotid intima-media wall thickness (CIMT) in ACS and controls.3. To investigate the associations between p66shc expression in PBMs and cardiovascular risk factors.4. To study the correlation between p66shc expression in PBMs and FMD, NID and CIMT. Discover the role of p66shc in endothelial dysfunction and atherosclerosis, providing new evidence for the treatment of ACS.Method:The study included consecutive patients at our hospital in2012, undergoing diagnostic coronary angiography because of suspected ACS, in which38patients were diagnosed with ACS,26male,12female, mean age58.1±7.6y. The diagnosis of ACS was according to typical clinical manifestation, signs, myocardial enzymes, myocardial troponin, electrocardiogram and the report of coronary angiography, corresponding to the acute coronary syndrom diagnostic criteria of WHO. There were36controls which included check-up crowd and patients with normal coronary angiographic reports,23male,13female, mean age54.6±7.6. All the controls were without history of coronary heart disease, rheumatic heart disease, cardiomyopathy, autoimmune disease, infectious disease performance, no hepatic and renal disease. Ten microlitre venous blood was drawn from all subjects under standardized conditions after a12h fast. Monocytes were extracted and serum was collected. The expression of p66shc mRNA was measured by RT-qPCR. The level of p66shc protein was detected by Western Blot. The level of serum homocysteine (Hcy) was detected by HPLC. Among74subjects,40(20ACS patients and20controls) were in stable condition and agree to detect the FMD, NID and CIMT, using high resolution ultrosound. Statistical analysis: The data were analyzed using SPSS17.0. The descriptive data were expressed as the means±standard deviations (SD). Independent-samples T Test, one-way ANOVA or χ2test were used for the comparisons between two groups. The descriptive data was assessed using linear correlation analysis, partial correlation analysis or multivariate line regression analysis. The correlation between the counting data was evaluated using Spearman correlation analysis. Differences with P<0.05were considered statistically significant.Result:1. The expression of p66shc mRNA (evaluate by RQ) in PBMs was significantly increased in patients with ACS than controls (1.36±0.74vs0.94±0.51,P=0.007). The expression of p66shc protein in PBMs was also significantly increased in ACS patients, when comparing with controls (1.40±0.10vs1.03±0.08, P=0.001).2. Both FMD and NID were significantly decreased in patients with ACS than in controls ((8.72±5.03)%vs13.74±2.31)%, P<0.001;(11.80±5.15)%vs (15.36±3.28)%, P=0.013)). CIMT of patients with ACS was more thicker than controls (0.82±0.26(cm) vs0.63±0.16(cm), P=0.007).3. There were a significant negative correlation between the FMD, NID and the expression of p66shc mRNA in PBMs (r=-0.910, P<0.001; r=-0.825, P<0.001), and a significant correlation between the expression of p66shc mRNA in PBMs and CIMT (r=0.627, P<0.001). After corrected by the effect of age, body mass index (BMI), triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and Hey, partial correlation analysis showed that there were still a significant negative correlation between the FMD, NID and the expression of p66shc mRNA in PBMs (r=-0.610, P<0.001; r=-0.442,P=-0.01), while the correlation was not exist between the CIMT and expression of p66shc mRNA in PBMs (r=0.289, P=0.102).4. Multivariate line regression analysis showed that there were significant correlations between LDL-C, Hey, FMD and the expression of p66shc mRNA in PBMs, the regression equation is YA=0.650+0.229LDL-C+0.062Hcy-8.100FMD. Conclusion:1. Both p66shc mRNA and protein expression in PBMs were increased in patients with ACS which suggests that p66shc participate in the pathogenesis of ACS through oxidative stress.2. There are correlations between FMD, NID, CIMT and the expression of p66shc mRNA in PBMs and these hints p66shc play a role in human vascular endothelial dysfuction and the formation of atherosclerosis.3. LDL-C, Hcy and FMD are the independent effecting factors of p66shc. |
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