Taurine protects against low-density lipoprotein-induced endothelial dysfunction by the DDAH/ADMA pathway.
Asymmetric dimethylarginine (ADMA), a major endogenous nitric oxide (NO) synthase inhibitor, is thought to be a key contributor for endothelial dysfunction. Decrease in activity of dimethylarginine dimethylaminohydrolase (DDAH), a major hydrolase of ADMA, causes accumulation of ADMA in some risk factors of atherosclerosis, including hypercholesterolemia. Taurine is a semi-essential amino acid that has previously been shown to have endothelial protective effects. The present study was to test whether the protective effect of taurine on endothelial function is related to modulation of the DDAH/ADMA pathway. A single injection of native LDL (4 mg/kg, i.v.) markedly reduced endothelium-dependent vasorelaxation and the plasma level of NO, and increased plasma concentrations of ADMA, malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-alpha). Treatment with taurine in vivo (60 or 180 mg/kg) significantly attenuated the inhibition of endothelium-dependent vasorelaxation and the reduced level of NO, and decreased the elevated levels of ADMA, MDA, and TNF-alpha. Incubation human umbilical vein endothelial cells (HUVECs) with ox-LDL (100 microg/ml) for 24 h markedly increased the medium levels of lactate dehydrogenase (LDH), ADMA, TNF-alpha and MDA, and decreased the level of NO in the medium and the intracellular activity of DDAH. Taurine (1 or 5 microg/ml) significantly attenuated the increases in the levels of LDH, ADMA, TNF-alpha and MDA, and the decrease in the level of NO and the activity of DDAH induced by ox-LDL in HUVECs. The present results suggested that taurine protected against endothelial dysfunction induced by native LDL in vivo or by ox-LDL in endothelial cells, and the protective effect of taurine on the endothelium is related to decrease in ADMA level by increasing of DDAH activity.
Tan
Bin
B
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #110, Changsha 410078, China.
Jiang
De-Jian
DJ
Huang
Huang
H
Jia
Su-Jie
SJ
Jiang
Jun-Lin
JL
Hu
Chang-Ping
CP
Li
Yuan-Jian
YJ
D000109:Acetylcholine / Q000494:pharmacology; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D002317:Cardiovascular Agents; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D013654:Taurine; D009569:Nitric Oxide; D008315:Malondialdehyde; C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase; D000109:Acetylcholine