The Roles And Of LPL And HL In The Progres Of Atherosis--Mechanism And Intervention

Background: The biological function of lipoprotein lipase (LPL) consists of two aspects. In plasm, LPL palys an important role in triglycerides hydrolysis, but at cell membrane of macrophages, LPL accelerates the foam cell transformation. Hepatic lipase (HL) acts a crucial role in the catabolism of cholesterol cleared by liver cell. However, in the pathological process of atherosclerosis, the metabolism and regulating factors of LPL and HL are unclear, the effects of modifying LPL and HL on AS are not elucidated.Aim: ①To study the metabolic mechanism of LPL and HL in the pathological process of atherosclerosis;②To investigate the effect of insulin on the LPL metabolism and the atherogenic mechanism of it;③To investigate the effect of tea-polyphenols on LPL and HL metabolism and its role in prevention and treatment of atherosclerosisMethods: The major experimental objects were AS rabbit model, THP-1 cell,HepG2 cell; the intervention factors included tea-polyphenols, insulin, VLDL, LDL, ox-LDL. The LPL and HL activity, the LPL mRNA and HL mRNA expression, foam cell and the area of atherosclerosis plaque were detected. Histochemistry technic, immunohistochemistry technic,RT-PCR were used respectively in the experiment.Results and Conclusion: 1. In AS rabbits, the TC,TG,LDL-c level in plasm were significant higher, the area of atherosclerosis plaque were more larger and the HL activity was more depressed than control group. The LPL and HL activity in the plasm was non significant difference between AS and control group.2. The similar expression of LPL mRNA in circulating white blood cells was detected in health and patients with coronary atherosclerotic disease.The level of LPL mRNA expression was not correlated with the serum lipid level and the severity of coronary stemosis. 3. In the process of foam cell formation, the expression of LPL mRNA, NF-κB and TGF-β1 mRNA in THP-1 cells induced by VLDL,LDL and ox-LDL were up-regulated significantly.4.High concentration of VLDL ,LDL and ox-LDL decreased the HL mRNA expression and HL activity in HepG2 cells. There was negative correlation between HL activity of HepG2 cells and the concentration of VLDL and LDL. 5. Ox-LDL strongly inhibits the cellproliferation , HL activity and the HL mRNA expression in HepG2 cells, it up-regulates the expression of NF-κB and TGF-β1 mRNA in THP-1 cells.These effects of ox-LDL were all stronger than that of VLDL and LDL. 6. Insulin enhances transferring THP-1 cells to foam cell exposed to ox-LDL, it also up-regulates LPL mRNA expression in the THP-1 cell . 7.After feeding AS rabbits with tea-polyphenols, the level of TC and LDL-c in serum, the area of atherosclerosis plaque on the aortic tunica intima and MDA in liver were significantly decreased, while HL activity in liver was significantly increased. 8. In THP-1 cells incubated with VLDL or LDL, the expression of NF-κB, LPL mRNA and TGF-β1mRNA were suppressed and the foam cell formation were decreased by tea-polyphenols(≤40ng/ml). In HepG2 cells incubated with ox-LDL, the HL activity was increased and HL mRNA expression was up-regulated after treating with tea-polyphenols(≤40ng/ml) .But tea-polyphenols(≤40ng/ml) did not suppresse the cell proliferation.