Lipoprotein Uptake and Degradation by Cultured Human Arterial Smooth Muscle Cells

Abstract

The multipotential smooth muscle cell (SMC) is the predominant cell in intima and media of large arteries, proliferating early in the development of atheroma to become the lipid-laden foam cell. Homogeneous cultures of human SMC have now been successfully grown from explants of normal pieces of artery obtained during surgery. In contrast to previous results with rat SMC, human SMC preferentially bind and take up large, lipid-rich lipoproteins (I¹²⁵ labeled low density and very low density lipoproteins) (LDL and VLDL), in comparison to smaller, high density lipoproteins (HDL). This species selectivity appears to be related to differences both in cells and in lipoproteins. Specific binding of lipoproteins by SMC, analyzed by release of radioactive protein from the cell surfaces by trypsin, accounted for approximately half of the protein radioactivity associated with the cell layer during the first few hours of incubation. Specific binding appears to be related to the presence of apoprotein B on the lipoproteins. Lipoproteins progressively accumulate within cells as a function of incubation time. Lipoprotein degradation, assessed by appearance of TCA soluble, non-iodide radioactivity in the incubation medium, increased rapidly after an initial delay of 2 to 4 hours. Cells grown under hypoxic (5% O₂) conditions instead of the usual room air showed impaired degradation of lipoproteins. These results suggest that there are receptors on arterial SMC, highly specific for different lipoproteins (as shown for skin fibroblasts). This tissue culture system may be useful for assessment of the effects of a variety of hormones, metabolites, and drugs on the handling of lipoproteins by arterial smooth muscle cells.