Departamento de Gastroenterología, Escuela de Medicina. Pontificia Universidad Católica de Chile. Santiago, Chile.
Ann Hepatol. 2017 Nov;16(Suppl. 1: s3-105.):s83-s86. doi: 10.5604/01.3001.0010.5500.
The recent discovery of bile acid (BA) receptors and a better delineation of the multiple roles of BAs in relevant biological processes have revamped BA research. The vasoactive actions of BAs were recognized more than three decades ago but the underlying mechanisms of the BA-induced vasorelaxation are now being clarified. Recent evidence shows that the BA receptors FXR and TGR5 are expressed in endothelial cells and may have important effects on both systemic and portal circulation. The availability of genetically engineered mice with ablation of BA receptors and the development of BA receptor agonists has allowed to explore the modulation of XR and, in a lesser extent, of TGR5 in the setting of portal hypertension (PHT) with promising results. In this review, we summarize recent data on how BA-dependent pathways influence several processes that impact in PHT and the preclinical data showing that pharmacological modulation of those pathways may hold promise in the treatment of PHT.
近年来,胆酸(BA)受体的发现以及对 BA 在相关生物过程中多种作用的更好描述,推动了 BA 研究的发展。三十多年前就已经认识到了 BA 的血管活性作用,但现在正在阐明 BA 诱导的血管舒张的潜在机制。最近的证据表明,BA 受体 FXR 和 TGR5 在内皮细胞中表达,并且可能对全身和门静脉循环都有重要影响。具有 BA 受体缺失的基因工程小鼠的可用性以及 BA 受体激动剂的开发,使得能够在门静脉高压症(PHT)的背景下探索 XR 的调节,并且在较小程度上探索 TGR5 的调节,这取得了有前景的结果。在这篇综述中,我们总结了最近关于 BA 依赖性途径如何影响影响 PHT 的几个过程的资料,以及显示这些途径的药理学调节可能有希望用于治疗 PHT 的临床前数据。