Density Lipoprotein Degradation Research Articles

Interactions Between Cultured Bovine Arterial Endothelial and Smooth Muscle Cells: Studies on Uptake and Degradation of Low Density Lipoproteins by Smooth Muscle Cells

This study was designed to investigate the effects of substances released from non-injured and injured bovine arterial endothelial cells on 125I-low density lipoprotein uptake and degradation by smooth muscle cells in culture. It was demonstrated that endothelial cell-released non-dialysable (molecular weight cut off 12-14000) substances significantly stimulated 125I-low density lipoprotein uptake and degradation by smooth muscle cells. Endothelial cell-released dialysable substances and endothelin-1 did not cause this stimulation. The increase in 125I-low density lipoprotein uptake and degradation by smooth muscle cells could be dissociated from cell proliferation. However, in endothelial cell-smooth muscle cell co-culture 125I-low density lipoprotein uptake and degradation by smooth muscle cells were not stimulated. Injury to endothelial cells by lipid-soluble smoke particles or ultraviolet light, which reduced total cellular protein by 15-25%, enhanced the endothelial cell release of the substances stimulating 125I-low density lipoprotein uptake. The results are discussed in relation to atherogenesis.

EXPOSURE TO LONG WAVELENGTH ULTRAVIOLET RADIATION DECREASES PROCESSING OF LOW DENSITY LIPOPROTEIN BY CULTURED HUMAN FIBROBLASTS

Exposure of MRC5 human fibroblasts to UVA radiation (365 nm) resulted in a dose-dependent decrease in low density lipoprotein (LDL) uptake and degradation by cells. Following a 25 J/cm2 irradiation dose, about 45% and 70% reduction in 125I-LDL uptake and degradation were observed, respectively. Under the same conditions, the 14C-sucrose uptake was also decreased to about the same extent as LDL uptake. Cell pretreatment with the antioxidants vitamin E and vitamin C did not prevent the UVA-induced fall in LDL degradation. These results point to the possible effects of UVA radiation on receptor-mediated and nonspecific uptake of exogenous molecules. With special regard to the alterations in receptor-mediated processing of exogenous ligands, such a phenomenon could be of importance in UVA-induced skin degenerative processes.

Heparin-binding growth factor type one and platelet-derived growth factor are required for the optimal expression of cell surface low density lipoprotein receptor binding activity in human adult arterial smooth muscle cells

Purified heparin-binding growth factor-1 (HBGF-1) stimulated low density lipoprotein binding, internalization, and degradation in isolated human adult arterial smooth muscle cells. Exposure of quiescent cells to HBGF-1 in serum-free, defined medium increased both low density lipoprotein (LDL) receptor activity and de novo cholesterol biosynthesis. Both events preceded the onset of DNA synthesis by 6 to 9 h. HBGF-1 acted additively with platelet-derived growth factor (PDGF) to maximally stimulate cell surface LDL receptor binding activity and DNA synthesis in the smooth muscle cells. The presence of LDL was required for maximal mitogenic activity of HBGF-1 and PDGF. In the presence of LDL, growth factor-stimulated, proliferating human smooth muscle cells accumulated cholesterol ester and triglycerides. The results suggest that HBGF-1, PDGF, and LDL act together to promote the maximal proliferation of smooth muscle cells in culture. Chronic exposure to the three growth promoters may contribute to the smooth muscle cell hyperplasia and lipid accumulation observed in atherosclerotic lesions.

Regulation of low density lipoprotein uptake and degradation in different animals species.

These various observations suggest that the intestinal-hepatic axis plays a key role in the regulation of cholesterol balance in the whole animal and the circulating levels of LDL-cholesterol. Nearly all sterol which enters or leaves the body must do so through the intestine and liver. Changes in the rate of entry or exit of cholesterol (or bile acids) from the animal are met by appropriate reciprocal changes in the rates of cholesterol synthesis in these two organs. As long as these adaptive changes in synthesis are adequate to meet the changing needs for cholesterol in the animal, the rates of receptor-mediated LDL degradation by the liver and intestine remain essentially unchanged as does the plasma LDL-cholesterol concentration. Only when the changes in cholesterol synthesis are inadequate to meet the changing sterol needs (or are blocked by drug administration (22] does the liver increase its rate of receptor-mediated LDL uptake which, in turn, results in significant alterations in circulating plasma LDL-cholesterol levels.