Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
J Nutr. 2010 Jan;140(1):12-7. doi: 10.3945/jn.109.110981. Epub 2009 Nov 18.
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 micromol/L of RTV and/or equol in concentrations of 0.1, 1, and 10 micromol/L for 24 h. 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.
HIV 蛋白酶抑制剂（PI）利托那韦（RTV）可能通过氧化应激引起血管损伤。我们本研究的目的是确定大豆异黄酮染料木黄酮是否可以预防 RTV 引起的猪肺动脉和人肺动脉内皮细胞（HPAEC）的内皮功能障碍。新鲜的猪肺动脉环用 15 微摩尔/升的 RTV 和/或 0.1、1 和 10 微摩尔/升的染料木黄酮处理 24 小时。未给予任何染料木黄酮或 RTV 的对照。基于肌动描记张力分析，与未处理的血管相比，RTV 显著降低了对血管环中缓激肽的内皮依赖性松弛，而抗氧化剂染料木黄酮以浓度依赖性方式有效逆转了 RTV 效应。RTV 还降低了对血栓烷 A2 类似物 U46619 的动脉环收缩，而染料木黄酮阻断了这种降低作用。此外，RTV 处理显著降低了猪肺动脉和 HPAEC 中内皮型一氧化氮合酶（eNOS）的表达，而染料木黄酮有效阻断了 RTV 诱导的 eNOS 下调。此外，RTV 显著增加超氧阴离子的产生，而染料木黄酮逆转了 RTV 在猪肺动脉中的这种作用。因此，抗氧化剂染料木黄酮通过减少 RTV 引起的血管舒缩功能障碍、eNOS 下调和氧化应激，有效保护血管功能免受 HIV PI RTV 的有害影响，在猪肺动脉和 HPAEC 中均具有保护作用。这些新数据表明，染料木黄酮可能在预防 HIV 相关心血管并发症方面具有临床应用价值。
