The Study Of The Effects Of Atorvastatin On Serum Lipids And Endothelial Lipase Gene Expression In Patients With Coronary Artery Disease

Background and PurposeIt is widely acknowledged that lowering low-density lipoprotein cholesterol in circulation can decrease risk of having coronary heart disease. However, more and more clinical evidences show that there is a certain risk to treat and prevent coronary heart disease by lowering LDL. It is found out by many previous randomized researches that high-density lipoprotein cholesterol level in serum has a negative correlation with cardiovascular disease occurrence. HDL itself has effects on anti-oxidation, anti-proliferation and anti-inflammation. Therefore, increasing HDL-C can be helpful in lowering risk of cardiovascular disease. In recent stage, the treatment of increasing HDL-C still has some limitations. For example, niacin can increase HDL-C density appropriately but on the other hand face problem of tissue tolerance. Yet fibrates medicines are very much limited in adjusting HDL-C level for most patients. Some experiments prove that infusion therapy based on apolipoprotein A-1can help in slowing AS growth, but still has no improvement until now.The research shows that statins can synthesize HMG-CoA reductase by competitively inhibiting endogenous cholesterol, which is as reductase inhibator of A HMG-CoA. It can prevent metabolism of HMG-CoA in cells, making cholesterol synthesis in cells reduced, thus induce to stimulate numbers of receptor and activity growth of low density lipoprotein on membrane surface (mainly referring to liver cells). It can further promote intake and catabolism of LDL-C. What is more important is that statins can moderately increase HDL-C level in circulation at the same time. There is still a lot room for further research to prove that statins can improve HDL-C level.Endothelial lipase has become a new member of triglyceride lipase that has been discovered recently. The main characteristic of EL is phospholipase activity, which can adjust HDL-C level through enzymolysis, and become the decisive factor of HDL-C level. EL expression is affected and adjusted jointly by many factors. Tumor Necrosis Factor-α (TNF-α), interleukin-β (IL-(3) and biological mechanism can all induce EL mRNA of endothelial cells.This research aims to testify whether atorvastatin, represented by statins, can adjust HDL-C through moderating EL level of Plasma, doing randomized contrast experiments on targeted group, besides, make analysis of potential factors of Plasma El, and thus provide more experimental evidence to future clinical applications of such medicine.Methods1. Research objects115patients, who were diagnosed with coronary heart disease in Cardiovascular Department of Qi1u Hospital of Shandong University from September2008to September2010,and58volunteers in good health were chosen and taken into the research. All the patients were divided into three groups,67patients in the non-atorvastatin treatment group,48patients in atorvastatin intervention group, and58volunteers in the comparison group.2. Methods2.1Blood sample collection was conducted to all patients according to treatment for every group after clinical treatment for three months. Blood specimen collection was conducted to patients in control group in same period of time. Serum and plasma will be reserved for future use.2.2Biochemical Indexes Analysis was conducted to detect triglycerides (TG)、total cholesterol (TC)、HDL-C、LDL-C、Apolipoprotein A1(apo-A1)、Apolipoprotein B (apo-B) and C-reactive protein by using automatic biochemical analyzer.2.3Fluorescence Quantitative PCR was applied to measure plasma IL-1/6、TNF-α and EL mRNA expression on the certain quantity.(1):to synthesize IL-1/6、TNF-α and EL mRNA primers.(2):to extract sum RNA of plasma and synthesize cDNA.(3):to test using Fluorescence Quantitative PCR.2.4Western Blot. Western Blot was used to measure plasma EL protein level of every group, using reserved plasma. Lysate was used to extract sum protein and measure extracted protein density. Plasma EL level was measured by half quantitative applying SDS-PAGE gel electrophoresis.2.5Above experimental statistics were analyzed using statistical methods.Results1. Serum Lipids of non-Atorvastatin:TC6.75±0.412、TG2.98±0.66、apo-B3.23±0.41、LDL-C4.93±1.09; atorvastatin treatment group:TC4.86±0.32、TG1.52±0.59、apo-B1.21±0.22、LDL-C2.88±0.77:Serum Lipids of control group:TC4.17±0.27、TG1.70±0.63、apo-B0.87±0.11、LDL-C3.11±0.79。The average TC、TG、 apo-B and LDL-C of patients with coronary heart disease in atorvastatin intervention group decrease compared with patients’in general treatment group or control group. It has significant difference, because P value is less than0.05.2. non-Atorvastatin:EL mRNA79.50±5.28、E1/actin0.971±0.069; atorvastatin treatment group:EL mRNA60.22±4.36、El/actin0.763±0.052:control group:EL mRNA59.66±4.96、El/actin0.796±0.038。El level (EL mRNA and plasma free EL) of patients with coronary heart disease in atorvastatin intervention group decrease compared with patients’in general treatment group or control group. It has significant difference, because P value is less than0.05.3. Serum Lipids levels of non-Atorvastatin treatment group:apo-A11.14±0.06、 HDL-C1.20±0.28;Serum Lipids levels of Atorvastatin treatment group:apo-A12.89±0.53、HDL-C1.77±0.61; control group:apo-A11.07±0.19、HDL-C1.38±0.33.The serum content of apo-Al and HDL-C in atorvastatin intervention group increases compared with the other two groups. It has significant difference, because P value is less than0.05.4. inflammatory cytokines TNF-α、IL-1、IL-6mRNAof non-Atorvastatin treatment group:TNF-α1.82±0.31、IL-13.31±0.89、IL-6mRNA2.31±0.69and CRP16.13±3.18 inflammatory cytokines of Atorvastatin treatment group:TNF-α1.13±0.09、IL-12.34±0.71、IL-6mRNA1.41±0.29and CRP8.72±3.36; control group: TNF-α1.19±0.11、IL-1、2.38±0.69、IL-6mRNA1.38±0.21、and CRP8.26±3.26。 The Plasma IL-1/6and TNF-a mRNA in atorvastatin intervention group show lower expression (P value is less than0.05) compared with non-Atorvastatin treatment group.5. Single-factor analysis shows that diabetes, no-atorvastatin-treatment, IL-1, IL-6, TNF-amRNA high level have significant relevance with Plasma EL high level (P value is less than0.05). From the multiple factors analysis, it shows that atorvastatin treatment, IL-1/6and TNF-a level have become the independent factors that influenced EL expression.Conclusions1. Atorvastatin can intervene abnormal lipid, and significantly decrease plasma TC、TG、apo-B、LDL-C and increase apo-A1and HDL level.2. Atorvastatin can significantly inhibit EL mRNA synthesis and free EL content.3. Atorvastatin can significantly decrease C reactive protein and inflammation factors IL-1/6and TNF-α level in circulation.4. Single-factor analysis shows that diabetes, no-atorvastatin-treatment, IL-1, IL-6, TNF-αmRNA high level have significant relevance with Plasma EL high level (P value is less than0.05). From the multiple factors analysis, it shows that atorvastatin treatment, IL-1/6and TNF-α level have become the independent factors that influenced EL expression.