Sustained Static Pressure Accelerates Cholesterol Accumulation In Vascular Smooth Muscle Cells Induced By Oxidized Low Density Lipoprotein.

OBJECTIVE: To investigate the accelerative effect of sustained static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) induced by oxidized low density lipoprotein (Ox-LDL).METHODS: VSMCs line (A10) from mouse aorta were incubated with OX-LDL(50ug/ml) in a special incubator contenting 95% CO₂ and 5% air, in which the pressure was regulated from 0 to 180 mmHg. Cholesterol accumulation of VSMCs was detected by Oil Red O and HPLC. The protein levels and mRNA levels of caveolin-1, SREBP-1,ApoE and SR-B1 were analyzed by western blot and RT-PCR, respectively.RESULTS: Static pressure treatment (0, 60, 90, 120, 150, 180 mmHg for 48 hours) accelerated cellular cholesterol accumulation in VSMCs in present of Ox-LDL (50ug/ml) with a pressure-dependent manner. Oil Red O staining showed that there were more lipid-drops in VSMCs with static pressure than those without static pressure. The cellular contents of FC and TC were increased respectively from 60.5±2.8mg/g to 150.8±9.4mg/g, and from 92.3±2.1mg/g to 386.7±6.4mg/g .Western blot analysis showed that ox-LDL down-regulated the protein expressions of caveolin-1 and SREBP-1.SR-B1 Interestingly, static pressure treatment further decreased the expression of these proteins. The mRNA of apo E was also significantly down-regulated by static pressure.CONSULTS Sustained static pressure could accelerate cholesterol accumulation in vascular smooth muscle cells. Down-regulation of caveolin-1, SREBP-1 and Apo E may play important roles in mediating the effects of sustained static pressure.