Taurine rescues vascular endothelial dysfunction in streptozocin-induced diabetic rats: correlated with downregulation of LOX-1 and ICAM-1 expression on aortas.
Macroangiopathy is a major complication of diabetes mellitus in which dysfunction of vascular endothelium induced by excessive oxidative stress is an early and key determinant. As an endogenous antioxidant, taurine possesses endothelial protective effect in vitro. LOX-1 is an endothelial receptor for oxidized low-density lipoprotein (oxLDL) which might mediate endothelial dysfunction and subsequent atherogenesis in diabetes. We used streptozotocin-induced rats as models of type 1 diabetes to evaluate the protective effect of taurine against vascular endothelial dysfunction in type 1 diabetes and the possibly involved molecule mechanism. Eight male Wistar rats were used as normal control group. Sixteen diabetic rats induced by one single injection of streptozocin (60 mg/kg, i.p.) were randomly divided into two groups after the diabetes onset: diabetes mellitus group and taurine-treated diabetes group. 6 weeks afterward, endothelium-dependent vasodilation of isolated thoracic aorta, serum oxLDL and soluble intercellular adhesion molecule (sICAM-l) levels, LOX-1 and intercellular adhesion molecule (ICAM-1) expression on aortas were determined respectively. Streptozocin-induced diabetic rats were complicated with excessive oxidative stress and endothelial dysfunction: increased serum oxLDL and sICAM-1, inhibited endothelium-dependent vasodilator responses to acetylcholine (1 nM-0.1 microM). Simultaneously, LOX-1 and ICAM-1 expression were enhanced in aortas of diabetic rats; whereas blunted endothelium-dependent vasodilator responses to acetylcholine, increased serum oxLDL and sICAM-1 level as well as overexpression of LOX-1 and ICAM-1 were all attenuated significantly by taurine treatment. In conclusion, taurine improves vascular endothelial dysfunction induced by experimental type 1 diabetes and this effect might be associated with downregulation of LOX-1 and ICAM-1 expression on aortic vascular endothelium via its antioxidative property.
Wang
Li-jun
LJ
Department of Pediatrics, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Yu
Yong-hui
YH
Zhang
Li-gong
LG
Wang
Yi
Y
Niu
Na
N
Li
Qian
Q
Guo
Lei-ming
LM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D013654:Taurine / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000975:Antioxidants; D008077:Lipoproteins, LDL; C495136:OLR1 protein, rat; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; D014665:Vasodilator Agents; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D013654:Taurine; D000109:Acetylcholine