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Atherogenic levels of low-density lipoprotein increase endocytotic activity in cultured human endothelial cells. Am J Pathol 1992 Mar;140(3):551-8

Date

03/01/1992

Pubmed ID

1546741

Pubmed Central ID

PMC1886169

Scopus ID

2-s2.0-0026551211   30 Citations

Abstract

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.

Author List

Holland JA, Pritchard KA, Rogers NJ, Stemerman MB

Author

Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Arteriosclerosis
Cells, Cultured
Cytochalasin B
Cytoskeleton
Endocytosis
Endothelium, Vascular
Humans
Lipoproteins, LDL
Osmolar Concentration
Thymidine
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a