The Soybean Isoflavonoid Equol Blocks Ritonavir-Induced Endothelial Dysfunction in Porcine Pulmonary Arteries and Human Pulmonary Artery Endothelial Cells
The Soybean Isoflavonoid Equol Blocks Ritonavir-Induced Endothelial Dysfunction in Porcine Pulmonary Arteries and Human Pulmonary Artery Endothelial Cells
复制标题
DOI：
10.3945/jn.109.110981
复制
发表时间：
2010-01-01
影响因子：
4.2
通讯作者：
Chen, Changyi
中科院分区：
文献类型：
--
作者：
Cheng, Charlie;Wang, Xinwen;Chen, Changyi
HIV蛋白酶抑制剂（PI）利托那韦（RTV）可通过氧化应激引起血管损伤。我们在这项研究中的目的是确定雌马酚，大豆黄酮，是否可以防止RTV诱导的猪肺动脉和人肺动脉内皮细胞（HPAEC）的内皮功能障碍。用15 μ mol/L的RTV和/或浓度为0.1、1和10 μ mol/L的雌马酚处理新鲜猪肺动脉环。对照组设定为不施用任何量的雌马酚或RTV。基于肌张力分析，RTV显着降低血管环中的血管舒缓激肽的内皮依赖性舒张反应与未经处理的血管相比，而抗氧化剂雌马酚有效地逆转RTV的影响，在浓度依赖性的方式。RTV还减少了血栓素A（2）类似物U46619引起的动脉环收缩，这种减少被雌马酚阻断。此外，RTV治疗显着降低内皮型一氧化氮合酶（eNOS）在猪肺动脉和HPAEC的表达，而雌马酚有效地阻止RTV诱导的eNOS下调。此外，RTV显着增加超氧阴离子的产生，而雌马酚逆转RTV在猪肺动脉中的这种作用。因此，抗氧化剂雌马酚通过减少RTV诱导的血管功能障碍、eNOS下调和氧化应激，有效地保护猪肺动脉和HPAEC中的血管功能免受HIV PI RTV的有害影响。这些新的数据表明，雌马酚可能在预防艾滋病毒相关的心血管并发症的临床应用。J.营养140：12-17，2010.
HIV protease inhibitor (PI) ritonavir(RTV) may cause vascular injury through oxidative stress. Our purpose in this study was to determine whether equol, a soy isoflavone, could prevent RTV-induced endothelial dysfunction in porcine pulmonary arteries and in human pulmonary artery endothelial cells (HPAEC). Fresh porcine pulmonary artery rings were treated with 15 mu mol/L of RTV and/or equol in concentrations of 0.1, 1, and 10 mu mol/L for 24 In. A control was set with no amount of equol or RTV administered. Based on myograph tension analysis, RTV significantly reduced endothelium-dependent relaxation in response to bradykinin in the artery rings compared with untreated vessels, whereas the antioxidant equol effectively reversed the RTV effect in a concentration-dependent manner. RTV also reduced the contraction of artery rings in response to thromboxane A(2) analogue U46619 and this reduction was blocked by equol. In addition, RTV treatment significantly reduced endothelial nitric oxide synthase (eNOS) expression in both porcine pulmonary arteries and HPAEC, whereas equol effectively blocked RTV-induced eNOS downregulation. Furthermore, RTV significantly increased superoxide anion production, whereas equol reversed this effect of RTV in porcine pulmonary arteries. Thus, the antioxidant equol effectively protects vascular function from the detrimental effects of HIV PI RTV in both porcine pulmonary arteries and HPAEC via a reduction in the vasomotor dysfunction, eNOS downregulation, and oxidative stress induced by RTV. These novel data suggest that equol may have a clinical application in preventing HIV-associated cardiovascular complications. J. Nutr. 140: 12-17, 2010.