Wang Tao, Cunningham Alexis, Houston Kevin, Sharma Aditya M, Chen Lingdan, Dokun Ayotunde O, Lye R John, Spolski Rosanne, Leonard Warren J, Annex Brian H
Robert M Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.
Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Vasc Med. 2016 Apr;21(2):99-104. doi: 10.1177/1358863X15621798. Epub 2015 Dec 24.
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.
在大多数有症状的外周动脉疾病（PAD）患者中，为腿部供血的主要血管严重狭窄或闭塞，使得远端血流量取决于诱导血管生成和侧支血管形成的能力。目前，尚无改善缺血肢体灌注、从而直接治疗PAD主要问题的药物。我们团队最近在一个临床前小鼠PAD模型中的报告显示，白细胞介素-21受体（IL-21R）在缺血后肢肌肉的内皮细胞中上调。我们进一步表明，在该模型中IL-21R缺失导致灌注恢复受损。在我们的研究中，我们试图确定IL-21R是否存在于PAD患者缺血肌肉的内皮中。通过对人腓肠肌活检，我们发现与对照个体相比，PAD患者骨骼肌内皮细胞中IL-21R水平升高。有趣的是，PAD患者循环中的IL-21水平大约高1.7倍。这些数据提供了直接证据，表明IL-21R通路在PAD患者中确实上调。该通路可能作为一个可调节的治疗靶点。
