Focal toxicity of oxysterols in vascular smooth muscle cell culture. A model of the atherosclerotic core region.
Cell necrosis and reactive cellular processes in and near the atherosclerotic core region might result from short-range interactions with toxic lipids. To model these interactions in cell culture, focal crystalline deposits of cholestane-3 beta,5 alpha,6 beta-triol, 25-OH cholesterol, and cholesterol were overlaid by a collagen gel, on which canine aortic smooth muscle cells were seeded. Oxysterols, but not cholesterol, caused focally decreased plating efficiency and cell death, leading to the formation of a persistent circular gap in the cell culture. Cholestanetriol was largely removed from the culture dishes over 3 to 4 weeks, whereas cholesterol and 25-OH cholesterol were largely retained. Smooth muscle cells were motile even in proximity to oxysterol crystals, with occasional suicidal migration toward the crystals. Chemoattraction, however, could not be demonstrated. Despite toxicity, cholestanetriol did not appear to alter the fraction of cells exhibiting 3H-thymidine uptake, even in areas close to the crystals. Thus, oxysterols may be toxic to some cells, without causing major impairment of the migration and proliferation of nearby cells. This would allow the simultaneous occurrence of cell death and proliferation evident in atherosclerosis.
Guyton
J R
JR
Department of Medicine, Baylor College of Medicine, Houston, Texas.
Black
B L
BL
Seidel
C L
CL
D000818:Animals; D001011:Aorta / Q000032:analysis / Q000166:cytology / Q000187:drug effects; D001161:Arteriosclerosis / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D002777:Cholestanols / Q000032:analysis / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D006888:Hydroxycholesterols / Q000032:analysis / Q000633:toxicity*; D000960:Hypolipidemic Agents / Q000032:analysis / Q000633:toxicity*; D008858:Microscopy, Phase-Contrast; D009131:Muscle, Smooth, Vascular / Q000032:analysis / Q000166:cytology* / Q000187:drug effects
D002777:Cholestanols; D006888:Hydroxycholesterols; D000960:Hypolipidemic Agents; C000474:cholestane-3,5,6-triol; C007997:25-hydroxycholesterol; D004247:DNA