High-density lipoprotein antagonizes oxidized low-density lipoprotein by suppressing oxygen free-radical formation and preserving nitric oxide bioactivity.
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 microg/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 microg/ml) for only 30s 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.
Lee
Chii-Ming
CM
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.
Chien
Chiang-Ting
CT
Chang
Po-Yuan
PY
Hsieh
Mo-Ying
MY
Jui
Hsiang-Yiang
HY
Liau
Chau-Song
CS
Hsu
Su-Ming
SM
Lee
Yuan-Teh
YT
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D012078:Renal Artery Obstruction / Q000503:physiopathology / Q000517:prevention & control; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D012501:Saphenous Vein / Q000166:cytology; D014461:Ultracentrifugation; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D052250:Nitric Oxide Synthase Type III