摘要
慢性肾脏疾病(CKD)是大幅增加心血管疾病风险的一个因素,这一认知引发了一场紧张的科研研究,旨在确定具体参与CKD的心血管并发症发展的因素,并可通过新的药物治疗方法延迟或减少发病。这可能与硫酸吲哚酚(IS)相关。IS是一种来自吲哚的内源性分子,是肠道细菌的蛋白质代谢产物,其通过芳香烃受体(AhR)发挥作用。IS早期积累于肾脏,对心血管系统产生促炎症反应和其他不良反应,特别是促进动脉粥样硬化和动脉粥样硬化相关的动脉血管重构。此外,IS还导致肾脏损伤从而引起恶性循环。透析对IS的消除效果有限,但可以通过预防细菌产生吲哚或在肠道内吸收来降低IS水平。更有趣的是,虽然还是理论,IS的抑制活动可能是在细胞水平上通过抑制AhR结合或IS细胞内信号转导。因此,IS靶点可能成为降低CKD心血管负担的一种选择。
关键词: 动脉瘤,动脉粥样硬化,心血管疾病,慢性肾病,硫酸吲哚酚,炎症,治疗,毒素。
图形摘要
Current Drug Targets
Title:Indoxyl Sulfate: A Candidate Target for the Prevention and Treatment of Cardiovascular Disease in Chronic Kidney Disease
Volume: 16 Issue: 4
Author(s): Chiara Barisione, Giorgio Ghigliotti, Marco Canepa, Manrico Balbi, Claudio Brunelli and Pietro Ameri
Affiliation:
关键词: 动脉瘤,动脉粥样硬化,心血管疾病,慢性肾病,硫酸吲哚酚,炎症,治疗,毒素。
摘要: The awareness that chronic kidney disease (CKD) is a condition of dramatically increased cardiovascular risk has prompted an intense research activity, aimed at identifying factors that are specifically involved in the development of cardiovascular complications of CKD and that can be delayed or reduced by novel pharmacological approaches. This may be the case with indoxyl sulfate (IS). IS is an endogenous molecule derived from indole, a product of protein metabolism by intestinal bacteria, which acts via the aryl hydrocarbon receptor (AhR). IS accumulates early in CKD and exerts proinflammatory and other detrimental effects on the cardiovascular system, in particular promoting atherosclerosis and atherosclerosis-related arterial remodeling. Furthermore, IS also contributes to renal damage, thereby fueling a vicious circle. Dialysis is poorly effective in removing IS, but its levels can be lowered by preventing the bacterial generation of indole or by absorbing this latter within the intestine. More intriguing, although still theoretical, is the possibility of inhibiting the action of IS at the cell level, by antagonizing the binding to AhR or IS intracellular signaling. Therefore, IS targeting might become an option for reducing the cardiovascular burden of CKD.
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Cite this article as:
Chiara Barisione, Giorgio Ghigliotti, Marco Canepa, Manrico Balbi, Claudio Brunelli and Pietro Ameri , Indoxyl Sulfate: A Candidate Target for the Prevention and Treatment of Cardiovascular Disease in Chronic Kidney Disease, Current Drug Targets 2015; 16 (4) . https://dx.doi.org/10.2174/1389450116666141230114500
DOI https://dx.doi.org/10.2174/1389450116666141230114500 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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