Taurine Protects Against Low-density Lipoprotein-induced Endothelial Dysfunction By The DDAH/ADMA Pathway

Oxide low-density lipoprotein(ox-LDL)is an important factor contributing the development of atherogenesis.L-arginine congener compounds asymmetric dimethylarginine(ADMA),an endogenous inhibitor of nitric oxide synthase(NOS),inhibit nitric oxide(NO) production.Our previous work has showed that a single injection of low-density lipoprotein(LDL)significantly increases the serum level of endogenous ADMA concomitantly with endothelial dysfunction: Incubation human umbilical vein endothelial cells(HUVECs)with ox-LDL,dimethylarginine dimethylaminohydrolase(DDAH),a major hydrolase of ADMA were devitalization,and cause accumulation of ADMA.Taurine is a sulfur-containing semiessential amino acid,an antioxidant and anti-inflammatory drug.Recently it has been reported that taurine preserves endothelial function and inhibit atherogenesis. However,the mechanisms responsible for the beneficial effect of taurine on endothelial cells remain unclear.Based on the elevated level of ADMA by lipid peroxides and antioxidant properties of taurine,in the present study we tested the protective effect of taurine on damages of the endothelium induced by Low-density lipoprotein(LDL),and whether the protective effect of taurine is related to the DDAH/ADMA pathway.METHODS:study were divided to two part.(1)Animal treatment: Blood samples were collected from carotid artery.Vasodilator responses to acetylcholine(Ach)in the isolated aortic rings were determined,and serum concentrations of asymmetric dimethylarginine(ADMA), malondialdehyde(MDA),tumour necrosis factor-α(TNF-α),Nitric oxide (NO).(2)Cell culture and treatment:Incubation human umbilical vein endothelial cells(HUVECs)with ox-LDL(100μg/ml)for 24h,the medium levels of lactate dehydrogenase(LDH),ADMA,TNF-α,NO, MDA and the intracellular activity of DDAH were measured.RESULTS:(1)A single injection of LDL(4mg/kg)significantly decreased vasodilator responses to Ach,increased the serum level of ADMA,MDA and TNF-α,and decreased the serum level of NO.Taurine (60 or 180mg/kg)markedly reduced the inhibition of vasodilator responses to Ach by LDL,and the protective effect of taurine at the high dose was greater compared with the lower group.Taurine inhibited the increased level of ADMA,MDA and TNF-αinduced by LDL,and increased the serum level of NO.(2)Incubation human umbilical vein endothelial cells(HUVECs)with ox-LDL(100μg/ml)for 24h,Taurine (1 or 5μg/ml)markedly decreased the medium levels of LDH,ADMA, MDA and TNF-α,and increased the level of NO in the medium and the intracellular activity of DDAH.CONCLUSIONS:taurine protects the endothelium against damages elicited by LDL in vivo and in culture,and the protective effect of taurine on endothelium is related to the DDAH/ADMA pathway.