Targeting cytokine signaling in salt-sensitive hypertension
Targeting cytokine signaling in salt-sensitive hypertension
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DOI：
10.1152/ajprenal.00273.2016
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发表时间：
2016-12-01
影响因子：
4.2
通讯作者：
Jeffs, Alexander D.
中科院分区：
文献类型：
--
作者：
Crowley, Steven D.;Jeffs, Alexander D.
激活的免疫细胞群部分通过刺激肾脏损伤和引起肾单位中不适当的钠重吸收而导致高血压。由T淋巴细胞和巨噬细胞产生的称为细胞因子的炎症介质作用于肾脏中的特异性钠转运蛋白，增强其活性或表达，从而导致血管内液体体积和心输出量的扩张。这些细胞因子的重叠功能，其中每一个都可以激活多种受体，在精确靶向高血压中的炎症信号级联方面提出了挑战。此外，广泛的免疫抑制可能使高血压患者暴露于不成比例的感染或恶性肿瘤风险。尽管如此，通过血压依赖性和非依赖性机制，明确的免疫调节治疗可能提供心血管和肾脏保护，这证明了对相关信号通路和组织部位进行全面调查的合理性，在这些部位中，炎性细胞因子发挥作用以夸大高血压的血压升高和靶器官损伤。
Activated immune cell populations contribute to hypertension in part through inciting damage to the kidney and by provoking inappropriate sodium reabsorption in the nephron. Inflammatory mediators called cytokines produced by T lymphocytes and macrophages act on specific sodium transporters in the kidney, augmenting their activity or expression, with consequent expansion of intravascular fluid volume and cardiac output. The overlapping functions of these cytokines, each of which may activate multiple receptors, present challenges in precisely targeting inflammatory signaling cascades in hypertension. Moreover, broad immune suppression could expose the hypertensive patient to disproportional risks of infection or malignancy. Nevertheless, the possibility that incisive immunomodulatory therapies could provide cardiovascular and renal protection through both blood pressure-dependent and - independent mechanisms justifies comprehensive investigation into the relevant signaling pathways and tissue sites in which inflammatory cytokines function to exaggerate blood pressure elevation and target organ damage in hypertension.