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

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

doi:10.1016/j.atherosclerosis.2005.03.029

« Previous Next »Atherosclerosis
Volume 183, Issue 2 , Pages 251-258, December 2005

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

Chii-Ming Lee
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7, Chung-Shan South Road, Taipei 100, Taiwan
Chiang-Ting Chien
- Departments of Medical Research, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7, Chung-Shan South Road, Taipei 100, Taiwan
Po-Yuan Chang
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7, Chung-Shan South Road, Taipei 100, Taiwan
Mo-Ying Hsieh
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7, Chung-Shan South Road, Taipei 100, Taiwan
Hsiang-Yiang Jui
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7, Chung-Shan South Road, Taipei 100, Taiwan
Chau-Song Liau
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7, Chung-Shan South Road, Taipei 100, Taiwan
Su-Ming Hsu
- Departments of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7, Chung-Shan South Road, Taipei 100, Taiwan
Yuan-Teh Lee
- Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7, Chung-Shan South Road, Taipei 100, Taiwan
- Corresponding author. Fax: +886 2 2395 9911.

Received 6 December 2004; received in revised form 25 January 2005; accepted 2 March 2005. published online 11 August 2005.

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 (100μg/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 (50μg/ml) for only 30s effectively reduced the level of free radicals generated by oxLDL or H₂O₂. 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.