Thiazolidinediones suppress endothelin-1 secretion from bovine vascular endothelial cells:: A new possible role of PPARγ on vascular endothelial function
Thiazolidinediones suppress endothelin-1 secretion from bovine vascular endothelial cells:: A new possible role of PPARγ on vascular endothelial function
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DOI：
10.1006/bbrc.1998.0126
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发表时间：
1999-01-27
影响因子：
3.1
通讯作者：
Watanabe, T
中科院分区：
文献类型：
--
作者：
Satoh, H;Tsukamoto, K;Watanabe, T
本实验观察了曲格列酮对培养的牛血管内皮细胞（bVEC）分泌内皮素-1（ET-1）的影响。胰岛素（10（-9）-10（-7）M）刺激内皮素-1（ET-1）分泌呈剂量依赖性，无动力学变化。（1-20 μ M）剂量依赖性地抑制自发和胰岛素刺激的ET-1分泌，曲格列酮的这种抑制作用与ET-1 mRNA水平的降低有关。添加吲哚美辛（100 μ M）或N-硝基-L-精氨酸甲酯（1 mM）和下调蛋白激酶C通过延长预处理的细胞与佛波酯，12-O-十四烷酰基佛波13-乙酸酯，没有影响曲格列酮的抑制作用，浓度高达10 μ M。曲格列酮没有改变细胞内钙离子浓度刺激血管紧张素II（10 μ M）。其他PPAR γ配体，吡格列酮（1-10 μ M）和15-脱氧-δ 12，14-前列腺素J（2）（1-10 μ M），但不是PPAR α配体，苯扎贝特（1-10 μ M），剂量依赖性地抑制bVEC的自发ET-1分泌。提示曲格列酮可能通过激活过氧化物酶体增殖物激活受体γ抑制内皮细胞ET-1 mRNA的表达和分泌，这种抑制作用可能与曲格列酮对胰岛素抵抗患者的治疗作用有关。(C)北京：科学出版社.
We examined the effect of troglitazone on immunoreactive endothelin-1 (ET-1) secretion from cultured bovine vascular endothelial cells (bVECs), Insulin (10(-9)-10(-7) M) stimulated ET-1 secretion in a dose-dependent fashion without any kinetic change, Troglitazone (1-20 mu M) dose-dependently inhibited both spontaneous and insulin-stimulated ET-1 secretion, This inhibitory effect of troglitazone was associated with reduced ET-1 mRNA levels. Addition of indomethacin (100 mu M) or Nw-nitro-L-arginine methyl ester (1 mM) and downregulation of protein kinase C by prolonged pretreatment of the cells with a phorbol ester, 12-O-tetradecanoylphorbol 13-acetate, did not affect the inhibitory effect of troglitazone at concentrations up to 10 mu M. Troglitazone did not change the intracellular Ca2+ concentration stimulated by angiotensin II (10 mu M). Other PPAR gamma ligands, pioglitazone (1-10 mu M) and 15-deoxy-delta 12, 14-prostaglandin J(2) (1-10 mu M), but not a PPAR alpha ligand, bezafibrate (1-10 mu M), dose-dependently suppressed spontaneous ET-1 secretion from bVECs, These results, taken together, suggest that troglitazone inhibits ET-1 mRNA expression and secretion in bVECs possibly through activation of PPAR gamma, This inhibition may contribute to the hypotensive effect of troglitazone in insulin-resistant subjects. (C) 1999 Academic Press.