School of Life Science, Beijing University of Chinese Medicine, Beijing, 100029, China.
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
Biomed Pharmacother. 2021 May;137:111264. doi: 10.1016/j.biopha.2021.111264. Epub 2021 Feb 23.
Retinoid X receptors (RXRs) are members of ligand-dependent transcription factors whose effects on a diversity of cellular processes, including cellular proliferation, the immune response, and lipid and glucose metabolism. Knock out of RXRα causes a hypoplasia of the myocardium which is lethal during fetal life. In addition, the heart maintains a well-orchestrated balances in utilizing fatty acids (FAs) and other substrates to meet the high energy requirements. As the master transcriptional regulators of lipid metabolism, RXRs become particularly important for the energy needs of the heart. Accumulating evidence suggested that RXRs may exert direct beneficial effects in the heart both through heterodimerization with other nuclear receptors (NRs) and homodimerization, thus standing as suitable targets for treating in cardiovascular diseases. Although compounds that target RXRs are promising drugs, their use is limited by toxicity. A better understanding of the structural biology of RXRs in cardiovascular disease should enable the rational design of more selective nuclear receptor modulators to overcome these problems. Here, this review summarizes a brief overview of RXRs structure and versatility of RXR action in the control of cardiovascular diseases. And we also discussed the therapeutic potential of RXR ligand.
视黄酸 X 受体（RXRs）是配体依赖性转录因子家族的成员，其对多种细胞过程有影响，包括细胞增殖、免疫反应以及脂质和葡萄糖代谢。RXRα 的敲除会导致心肌发育不良，在胎儿期就会致命。此外，心脏维持着利用脂肪酸（FAs）和其他底物来满足高能量需求的良好平衡。作为脂质代谢的主要转录调节因子，RXRs 对心脏的能量需求变得尤为重要。越来越多的证据表明，RXRs 可能通过与其他核受体（NRs）形成异二聚体和同二聚体来直接对心脏发挥有益作用，因此成为治疗心血管疾病的合适靶点。尽管靶向 RXRs 的化合物是有前途的药物，但由于毒性限制了它们的使用。更好地了解心血管疾病中 RXRs 的结构生物学，应能使我们合理设计更具选择性的核受体调节剂来克服这些问题。在这里，我们对 RXRs 的结构以及 RXRs 在控制心血管疾病中的作用的多功能性进行了简要概述。我们还讨论了 RXR 配体的治疗潜力。
