Atherogenic levels of low-density lipoprotein increase endocytotic activity in cultured human endothelial cells.
Cultured human umbilical vein endothelial cells (EC) exposed to atherogenic low-density lipoprotein (LDL) levels for protracted periods demonstrated heightened endocytosis. Confluent EC were incubated with LDL 90 to 240 mg/dl cholesterol for 1 to 4 days and endocytosis was measured by 14C-sucrose uptake. Control EC and cells incubated with 90 mg/dl LDL cholesterol showed similar uptakes of 14C-sucrose during all measured time periods. In contrast, EC exposed to 240 mg/dl LDL cholesterol showed an increase in endocytosis beginning at 2 days, whereas 160 mg/dl LDL cholesterol promoted increased uptake by 4 days. The endocytotic activity of LDL-perturbed EC is reduced to levels seen in control cells by cytochalasin B, an actin polymerization inhibitor. This finding suggests a modulatory role for the cytoskeleton in endocytosis changes. Examination of LDL-perturbed EC cytoskeleton reveals structural remodeling resulting in a marked increase in stress fibers. Cytochalasin B exposure causes a loss of stress fibers with the formation of globular filamental aggregates. Such LDL-induced cellular functional changes may contribute mechanistically to endothelial dysfunction, which is widely held to be a major contributing factor in the pathogenesis of atherosclerosis.
Holland
J A
JA
Department of Medicine, New York Medical College, Valhalla.
Pritchard
K A
KA
Rogers
N J
NJ
Stemerman
M B
MB
D001161:Arteriosclerosis / Q000139:chemically induced*; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008077:Lipoproteins, LDL; D009994:Osmolar Concentration; D013936:Thymidine / Q000378:metabolism
D008077:Lipoproteins, LDL; D003571:Cytochalasin B; D013936:Thymidine