Endothelial interleukin-21 receptor up-regulation in peripheral artery disease.
Endothelial interleukin-21 receptor up-regulation in peripheral artery disease.
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DOI：
10.1177/1358863x15621798
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Annex BH
中科院分区：
文献类型：
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作者：
Wang T;Cunningham A;Houston K;Sharma AM;Chen L;Dokun AO;Lye RJ;Spolski R;Leonard WJ;Annex BH
在大多数有症状的外周动脉疾病（PAD）患者中，供应腿部的主要血管严重狭窄或闭塞，使得远端血流的量取决于诱导血管生成和侧支血管形成的能力。目前，还没有药物可以改善缺血肢体的灌注，从而直接治疗PAD的主要问题。本课题组最近在临床前小鼠PAD模型中的报告显示，缺血后肢肌肉的内皮细胞中白细胞介素-21受体（IL-21 R）上调。我们进一步表明，在该模型中，IL-21 R的丧失导致灌注恢复受损。在我们的研究中，我们试图确定IL-21 R是否存在于PAD患者缺血肌肉的内皮中。通过人腓肠肌活检，我们发现PAD患者骨骼肌内皮细胞中IL-21 R水平高于对照组。有趣的是，PAD患者的循环IL-21水平高出约1.7倍。这些数据提供了直接证据，表明IL-21 R通路确实在PAD患者中上调。该途径可用作调节的治疗靶点。
In most patients with symptomatic peripheral artery disease (PAD), severe stenosis in or occlusion of the major blood vessels that supply the legs make the amount of distal blood flow dependent on the capacity to induce angiogenesis and collateral vessel formation. Currently, there are no medications that improve perfusion to the ischemic limb, and thus directly treat the primary problem of PAD. A recent report from our group in a pre-clinical mouse PAD model showed that interleukin-21 receptor (IL-21R) is up-regulated in the endothelial cells from ischemic hindlimb muscle. We further showed that loss of IL-21R resulted in impaired perfusion recovery in this model. In our study, we sought to determine whether IL-21R is present in the endothelium from ischemic muscle of patients with PAD. Using human gastrocnemius muscle biopsies, we found increased levels of IL-21R in the skeletal muscle endothelial cells of patients with PAD compared to control individuals. Interestingly, PAD patients had approximately 1.7-fold higher levels of circulating IL-21. These data provide direct evidence that the IL-21R pathway is indeed up-regulated in patients with PAD. This pathway may serve as a therapeutic target for modulation.