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慢性肾脏病中的动脉重塑:尿毒症毒素的影响及新的药理学方法

Arterial Remodelling in Chronic Kidney Disease: Impact of Uraemic Toxins and New Pharmacological Approaches.

作者信息

Foudi Nabil, Palayer Maeva, Briet Marie, Garnier Anne-Sophie

机构信息

INSERM, CNRS, MITOVASC, Equipe CarMe, SFR ICAT, Université Angers, F-49000 Angers, France.

Service de Pharmacologie-Toxicologie et Pharmacovigilance, Centre Hospitalo-Universitaire d'Angers, F-49000 Angers, France.

出版信息

J Clin Med. 2021 Aug 25;10(17):3803. doi: 10.3390/jcm10173803.

Abstract

Chronic kidney disease (CKD) is a major public health concern that affects around 10 percent of the world's population. The severity of CKD is mainly due to the high prevalence of cardiovascular (CV) complications in this population. The aim of this review is to describe the arterial remodelling associated with CKD, to provide a quick overview of the mechanisms involved and to review the recent pharmacological approaches aimed at improving vascular health in CKD. CKD patients are exposed to metabolic and haemodynamic disorders that may affect the CV system. Large artery functional and geometric abnormalities have been well documented in CKD patients and are associated with an increase in arterial stiffness and a maladaptive remodelling. Uraemic toxins, such as indoxyl sulphate, p-cresyl sulphate, protein carbamylation and advanced glycation products, exert various effects on vascular smooth muscle cell functions. The low-grade inflammation associated with CKD may also affect arterial wall composition and remodelling. It is worth noting that the CV risk for CKD patients remains high despite the pharmacological control of traditional CV risk factors, suggesting the need for innovative therapeutic strategies. An interventional study targeting the NLRP3 inflammasome has provided some interesting preliminary results that need to be confirmed, especially in terms of safety.

摘要

慢性肾脏病(CKD)是一个重大的公共卫生问题,影响着全球约10%的人口。CKD的严重性主要归因于该人群中心血管(CV)并发症的高患病率。本综述的目的是描述与CKD相关的动脉重塑,快速概述其中涉及的机制,并综述近期旨在改善CKD患者血管健康的药理学方法。CKD患者会面临可能影响心血管系统的代谢和血流动力学紊乱。大动脉功能和几何结构异常在CKD患者中已有充分记录,且与动脉僵硬度增加和适应性不良重塑有关。尿毒症毒素,如硫酸吲哚酚、对甲酚硫酸盐、蛋白质氨甲酰化产物和晚期糖基化终产物,对血管平滑肌细胞功能有多种影响。与CKD相关的低度炎症也可能影响动脉壁组成和重塑。值得注意的是,尽管对传统心血管危险因素进行了药物控制,但CKD患者的心血管风险仍然很高,这表明需要创新的治疗策略。一项针对NLRP3炎性小体的干预性研究提供了一些有趣的初步结果,但这些结果需要得到证实,尤其是在安全性方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1573/8432213/278f69e06808/jcm-10-03803-g001.jpg

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