Pyridoxine prevents dysfunction of endothelial cell nitric oxide production in response to low-density lipoprotein.
Low-density lipoprotein (LDL) inhibits endothelium-dependent vasorelaxation. The aim of this study was to determine whether pyridoxine supplementation improves indices of LDL-induced endothelial dysfunction. Human umbilical vein endothelial cells (HUVEC) were incubated with native LDL (nLDL) from healthy subjects, oxidized LDL (oxLDL, formed by nLDL oxidation) or nLDL from type II diabetic patients (dLDL), in the absence or presence of pyridoxine; nitric oxide synthase (NOS) activity, cyclic GMP and expression of NOS isoforms were measured, as well as thiobarbituric acid reactive substances (TBARS) in HUVEC supernatants and amino acid concentrations in HUVEC lysates. All LDL species inhibited total NOS activity, whilst increasing the much smaller Ca2+-independent component of NOS activity, the effects of oxLDL being greatest and those of nLDL smallest; in accordance with these findings, NOS type 3 expression decreased and NOS type 2 expression increased, with a resultant decrease in bioactive nitric oxide (NO), in HUVEC treated with each LDL species, with the same rank order of potency. LDL species also increased TBARS in HUVEC supernatants as well as homocysteine concentrations in HUVEC lysates, nLDL < dLDL < oxLDL. Pyridoxine largely prevented all LDL-induced changes in NOS activity and isoform expression, as well as in TBARS and homocysteine. The findings suggest that pyridoxine prevents LDL-induced dysfunction of endothelial cell NO generation, most likely through its antioxidant effects as well as through its effects on cellular homocysteine metabolism. This has important potential therapeutic implications for cardiovascular disease prevention.
Ji
Yong
Y
Institute of Reproductive Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing 210029, China. yongji@njmu.edu.cn
Diao
Jianxin
J
Han
Yi
Y
Huang
Yan
Y
Bai
Hui
H
Chen
Qi
Q
Fan
Leming
L
Ferro
Albert
A
D006152:Cyclic GMP / Q000032:analysis / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D011736:Pyridoxine / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology; D014803:Vitamin B Complex / Q000494:pharmacology*
D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D014803:Vitamin B Complex; D009569:Nitric Oxide; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP; D011736:Pyridoxine