Monash Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Baker Heart and Diabetes Research Institute, Melbourne, Victoria, Australia.
Toxicol Lett. 2019 Jun 15;308:34-49. doi: 10.1016/j.toxlet.2019.03.002. Epub 2019 Mar 11.
Cardiorenal syndrome (CRS) remains a global health burden with a lack of definitive and effective treatment. Protein-bound uremic toxin (PBUT) overload has been identified as a non-traditional risk factor for cardiac, renal and vascular dysfunction due to significant albumin-binding properties, rendering these solutes non-dialyzable upon the state of irreversible kidney dysfunction. Although limited, experimental studies have investigated possible mechanisms in PBUT-mediated cardiac, renal and vascular effects. The ultimate aim is to identify relevant and efficacious targets that may translate beneficial outcomes in disease models and eventually in the clinic. This review will expand on detailed knowledge on mechanisms involved in detrimental effects of PBUT, specifically affecting the heart, kidney and vasculature, and explore potential effective intracellular targets to abolish their effects in CRS initiation and/or progression.
心肾综合征（CRS）仍然是一个全球性的健康负担，缺乏明确和有效的治疗方法。由于显著的白蛋白结合特性，蛋白结合尿毒症毒素（PBUT）过载已被确定为心脏、肾脏和血管功能障碍的非传统危险因素，使这些溶质在不可逆肾功能障碍状态下不可透析。尽管有限，但实验研究已经研究了 PBUT 介导的心脏、肾脏和血管作用的可能机制。最终目的是确定相关的有效靶点，这些靶点可能在疾病模型中带来有益的结果，并最终在临床上转化。本综述将详细介绍 PBUT 对心脏、肾脏和血管的有害影响所涉及的机制，探讨潜在的有效细胞内靶点，以消除它们在 CRS 发生和/或进展中的作用。
