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Atherogenic levels of low‐density lipoprotein increase hydrogen peroxide generation in cultured human endothelial cells: Possible mechanism of heightened endocytosis
Author(s) -
Holland James A.,
Ziegler Linda M.,
Meyer Jamie W.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199601)166:1<144::aid-jcp17>3.0.co;2-f
Subject(s) - endocytosis , reactive oxygen species , hydrogen peroxide , umbilical vein , chemistry , low density lipoprotein , cholesterol , lipoprotein , oxidative stress , microbiology and biotechnology , endocrinology , medicine , biochemistry , biology , cell , in vitro
Cultured human umbilical vein endothelial cells (EC) exposed to atherogenic low‐density lipoprotein (LDL) levels have augmented reactive oxygen species generation. Confluent EC were incubated with 30–330 mg/dl LDL cholesterol and cellular hydrogen peroxide (H 2 O 2 ) generation measured. EC incubated with 30 and 90 mg/dl LDL cholesterol showed similar low level H 2 O 2 production. In contrast, EC exposed to 180 and 330 mg/dl LDL cholesterol have a marked, dose‐related elevation in H 2 O 2 generation. Subsequent studies have explored if direct EC exposure to H 2 O 2 promotes cellular functional changes similar to those induced by high LDL levels (> 160 mg/dl cholesterol). Confluent EC were incubated with 0.1–10 mM H 2 O 2 for 30 minutes and endocytosis measured and cytoskeletal structure examined. H 2 O 2 exposure (0.5 and 1 mM) promoted heightened EC endocytosis, which similarly occurs with high LDL exposure. Likewise, cytoskeletal examination of EC perturbed with 1 mM H 2 O 2 reveals structural remodeling with a marked increase in stress fibers, which similarly happens with high LDL levels. The above observations that high LDL levels cause increased EC H 2 O 2 production, and direct H 2 O 2 exposure promotes cellular functional changes similar to those induced by high LDL concentrations, suggest a modulatory role for reactive oxygen species. Thus LDL‐induced reactive oxygen species generation may contribute mechanistically to endothelial perturbation, which has been hypothesized to be a major contributing factor in the pathogenesis of atherosclerosis. © 1996 Wiley‐Liss, Inc.