Effect of abnormal hemodynamics on cholesterol metabolism of HUVEC and its mechanism in inducing atherosclerosis

Objective To investigate the effects of abnormal hemodynamics on the uptake, synthesis and efflux of cholesterol in human umbilical vein endothelial cells (HUVECs) and explore the role of abnormal hemodynamics and cholesterol metabolism in the formation of atherosclerosis. Methods When the cells grew well, a new culture solution containing low-density lipoprotein (LDL) and ATP binding cassette transporter A1 (ABCA1) was used, and pressure was added. According to the pressure used, the cells were randomly divided into four groups: a stress group, a wall pressure group, a control group A and a control group B. They were cultured for 24 h under corresponding pressures. Then, the cells and culture media were collected for later use. The LDL and cholesterol concentrations in the culture media of the four groups were detected by enzymatic method. The content of intracellular cholesterol and the content of cholesterol within cell membrane were determined by HPLC. The expression of low density lipoprotein receptor (LDLR), 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR) and ABCA1 mRNA and protein were detected by real-time quantitative RT-PCR and Western blot, respectively. Results Compared with the control group B, the content of LDL in the culture media of the stress group significantly decreased and the content of intracellular cholesterol increased. Moreover, the expression of LDLR and HMG-CR mRNA and protein significantly increased. In the wall pressure group, the cholesterol content in the culture media significantly increased, the cholesterol content within the cell membrane significantly decreased, and the expression of ABCA1mRNA and protein significantly increased. In the control group A, the LDL content significantly decreased and the cholesterol content significantly increased in the culture media, and the expression of LDLR, HMG-CR and ABCA1 mRNA and protein significantly increased. Conclusions Stress promotes the uptake of LDL and cholesterol synthesis by up-regulating the expression of LDLR and HMG-CR mRNA and protein, while wall pressure promotes cholesterol efflux by up-regulating the expression of ABCA1 mRNA and protein. Abnormal hemodynamics disturbs the cholesterol metabolism balance in vascular endothelial cells and causes AS.