© 1997 American Heart Association, Inc.
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Both Intracellular and Extracellular Vitamin C Inhibit Atherogenic Modification of LDL by Human Vascular Endothelial Cells
From the Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass.
Correspondence to Balz Frei, PhD, Linus Pauling Institute, Oregon State University, 571 Wenger Hall, Corvallis, OR 97331. E-mail balz.frei.{at}orst.edu
Abstract Oxidative modification of LDL by vascular cells has been proposed as a mechanism by which LDL becomes atherogenic. Antioxidants that can prevent LDL oxidation may therefore act as antiatherogens. We used endothelial cells (ECs) from human aortas (HAECs), human saphenous veins (HSECs), and bovine aortas (BAECs) to investigate the role of intracellular and extracellular vitamin C (ascorbate) in EC-mediated LDL modification. Incubation of LDL (0.1 mg protein per milliliter) with confluent HAECs in Ham's F-10 medium led to time-dependent modification of the lipoprotein. In contrast, incubation of LDL with HAECs in medium 199, which does not contain redox-active transition metal ions, did not lead to LDL modification. Both HAEC-mediated and cell-free LDL modifications in Ham's F-10 medium were strongly inhibited in a time- and dose-dependent manner by physiological concentrations of ascorbate. Confluent HAECs cultured under conventional conditions contained very little intracellular ascorbate (<0.5 nmol/mg protein) but could be loaded with up to 20 nmol ascorbate per milligram protein in a time- and concentration-dependent manner. Ascorbate-loaded HAECs exhibited a lower capacity to modify LDL than did non–ascorbate-loaded control cells. When LDL was incubated with HSECs instead of HAECs, similar time- and concentration-dependent inhibitory effects on LDL modification of intracellular and extracellular ascorbate were observed. In contrast to human ECs, BAECs did not take up vitamin C and therefore only coincubation but not preincubation with ascorbate inhibited BAEC-mediated LDL modification. Our data show that enrichment of human vascular ECs with vitamin C lowers their capacity to modify LDL. In addition, extracellular vitamin C strongly inhibits EC-mediated, metal ion–dependent atherogenic modification of LDL.
Key Words: modified LDL • metal ions • ascorbate • atherosclerosis • human endothelial cells
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