152

Biochimica et Biophysics 0 Elsevier/North-Holland

488 (1977) 152-160 Biomedical Press

Acta,

BBA 57003

REGULATION OF LOW DENSITY LIPOPROTEIN RECEPTOR ACTIVITY BY CULTURED HUMAN ARTERIAL SMOOTH MUSCLE CELLS

EDWIN L. BIERMAN and JOHN ALBERS Division of Metabolism, Endocrinology and Gerontology, Northwest Lipid Research Clinic Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195 (U.S.A.)

(Received December 29th, 1976)

Summary The ability of cultured human arterial smooth muscle cells to regulate low density lipoprotein (LDL) receptor activity was tested. In contrast to human skin fibroblasts incubated with lipoprotein deficient medium under identical conditions, smooth muscle cells showed significantly reduced enhancement of ‘*‘I-labeled LDL and ‘*‘I-labeled VLDL (very low density lipoprotein) binding. Smooth muscle cells also failed to suppress LDL receptor activity during incubation with either LDL or cholesterol added to the medium, while fibroblasts showed an active regulatory response. Thus, in comparison with the brisk LDL receptor regulation characteristic of skin fibroblasts, arterial smooth muscle cells have an attenuated capacity to regulate their LDL receptor activity. These results may be relevant to the propensity of these cells to accumulate LDL and cholesterol and form “foam cells” in the arterial wall in vivo, a process associated with atherogenesis. Introduction Cultured human skin fibroblasts from normal donors have been shown to possess specific high affinity receptors on their surface that bind plasma low density lipoprotein (LDL) [ 11. These receptors appear to be regulated by a feedback mechanism responsive to the LDL concentration in the surrounding medium [2]. Thus reduction of LDL in the medium leads to an increase in LDL binding, presumably mediated by lowering intracellular cholesterol content, and conversely, elevation of medium LDL will suppress LDL binding. Similar regulation of LDL receptor activity has recently been reported in freshly isolated human lymphocytes [3]. Brown and Goldstein have proposed that this receptor regulation serves to regulate the intracellular cholesterol content of cultured human fibroblasts [ 2,4]. Such a mechanism would prevent Abbreviations:LDL, proteins

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Regulation of low density lipoprotein receptor activity by cultured human arterial smooth muscle cells.

152 Biochimica et Biophysics 0 Elsevier/North-Holland 488 (1977) 152-160 Biomedical Press Acta, BBA 57003 REGULATION OF LOW DENSITY LIPOPROTEIN R...
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