High-density lipoprotein antagonizes oxidized low-density lipoprotein by suppressing oxygen free-radical formation and preserving nitric oxide bioactivity

Chii Ming Lee, Chiang-Ting Chien, Po Yuan Chang, Mo Ying Hsieh, Hsiang Yiang Jui, Chau Song Liau, Su Ming Hsu, Yuan Teh Lee

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The antiatherogenic role of high-density lipoprotein (HDL) has been related to its ability to increase the activity of endothelial nitric oxide synthase (eNOS) and to protect low-density lipoprotein (LDL) against oxidative modification. The present study was aimed to determine whether and how HDL antagonizes oxidized LDL (oxLDL) that has been formed and accumulated in circulation. Pre-infusion of rats with HDL effectively prevented oxLDL-induced renal vascular constriction. Consistently, pre-incubation of human saphenous vein endothelial cells with HDL (100 μg/ml) reversed the oxLDL-induced suppression of endothelium-dependent cyclic-GMP production in co-cultured smooth muscle cells. However, the changes of Akt phosphorylation and eNOS activity in endothelial cells in response to lipoprotein treatments under our assay condition were not significant. Intriguingly, pretreatment of human umbilical vein endothelial cells with HDL (50 μg/ml) for only 30 s effectively reduced the level of free radicals generated by oxLDL or H 2 O 2 . In kidneys of living rats, renal arterial infusion of oxLDL greatly enhanced ischemia/reperfusion-induced free radicals, which could be attenuated by HDL pretreatment. We conclude that HDL may antagonize oxLDL on endothelial function through an Akt-independent pathway in which HDL preserves nitric oxide bioactivity by attenuating oxLDL-triggered free radical generation.

Original languageEnglish
Pages (from-to)251-258
Number of pages8
JournalAtherosclerosis
Volume183
Issue number2
DOIs
Publication statusPublished - 2005 Dec 1

Keywords

  • Endothelial cells
  • Free radicals
  • High-density lipoprotein
  • Nitric oxide
  • Oxidized low-density lipoprotein

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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