抄録
We previously reported that hypoxic incubation (2% O2) promoted the cellular cholesterol (especially esterified form) accumulation in cultured rabbit arterial smooth muscle cells in the presence of diet induced hyperlipemic serum.
Present study was designed to examine cholesterol and other lipids accumulation in cultured rabbit fibroblasts under different degree of hypoxic conditions (2% O2 and 5% O2), and to investigate the role of LDL-receptor in cellular lipids accumulation using cultured fibroblasts from WHHL-rabbit.
After 48 hours incubation of normal fibrobasts in the medium with 20% normolipemic rabbit serum (NLS), free fatty acid level increased slightly and triglyceride level increased markedly in hypoxic group. While in the medium with 20% hyperlipemic rabbit serum (HLS), in addition to the increased free fatty acid and triglyceride levels, free cholesterol level increased slightly and esterified cholesterol level increased markedly in hypoxic group. And these increases were correlated with O2 concentration inversely.
Moreover, in WHHL fibroblasts, which lacked LDL-receptor, cellular lipids accumulation were also observed after 48 hours incubation in the medium with 20% HLS, and hypoxic incubation enhanced the cellular lipids accumulation, as in normal fibroblasts.
These results suggest that under hyperlipemic condition, receptor non-mediated uptake of lipoproteins plays an important role in cellular lipids deposition in peripheral cells, and tissue hypoxia may promote the lipids accumulation in peripheral cells including vascular smooth muscle cells by LDL-receptor independent mechanism.