Jha Prabhash Kumar, Nakano Toshiaki, Itto Lucas Yuji Umesaki, Barbeiro Miguel Cantadori, Lupieri Adrien, Aikawa Elena, Aikawa Masanori
Center for Excellence in Vascular Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Front Cardiovasc Med. 2025 Mar 25;12:1574489. doi: 10.3389/fcvm.2025.1574489. eCollection 2025.
Chronic kidney disease (CKD) is a progressive condition characterized by the gradual loss of kidney function, leading to the accumulation of uremic toxins in the bloodstream. These toxins play a pivotal role in mediating vascular inflammation, a key contributor to the high cardiovascular morbidity and mortality observed in CKD patients. This review article explores the intricate mechanisms by which uremic toxins accelerate vascular inflammation. Macrophages, as versatile immune cells, are central to the inflammatory response. Evidence suggests that the uremic milieu influences macrophage biology. In this review article, we focus on the signaling through which uremic toxins, particularly indoxyl sulfate-an independent risk factor for cardiovascular complications in CKD patients, modulate macrophage activation and function, and how these changes contribute to vascular inflammation, leading to the increased cardiovascular risk. Investigation of such mechanisms provide molecular bases for the development of new therapies that retard the development of cardiovascular disorders in CKD patients.
慢性肾脏病(CKD)是一种渐进性疾病,其特征是肾功能逐渐丧失,导致血液中尿毒症毒素蓄积。这些毒素在介导血管炎症中起关键作用,而血管炎症是CKD患者心血管发病率和死亡率高的一个关键因素。这篇综述文章探讨了尿毒症毒素加速血管炎症的复杂机制。巨噬细胞作为多功能免疫细胞,是炎症反应的核心。有证据表明,尿毒症环境会影响巨噬细胞生物学特性。在这篇综述文章中,我们重点关注尿毒症毒素,尤其是硫酸吲哚酚(CKD患者心血管并发症的一个独立危险因素)通过何种信号传导调节巨噬细胞的激活和功能,以及这些变化如何导致血管炎症,进而增加心血管风险。对这些机制的研究为开发延缓CKD患者心血管疾病发展的新疗法提供了分子基础。