肾移植后的急性排斥反应与循环微小RNA及血管损伤相关。
Acute Rejection After Kidney Transplantation Associates With Circulating MicroRNAs and Vascular Injury.
作者信息
Bijkerk Roel, Florijn Barend W, Khairoun Meriem, Duijs Jacques M G J, Ocak Gurbey, de Vries Aiko P J, Schaapherder Alexander F, Mallat Marko J K, de Fijter Johan W, Rabelink Ton J, van Zonneveld Anton Jan, Reinders Marlies E J
机构信息
Department of Internal Medicine (Nephrology), Leiden University Medical Center, The Netherlands.
Einthoven Laboratory for Experimental Vascular Research, Leiden University Medical Center, The Netherlands.
出版信息
Transplant Direct. 2017 Jun 19;3(7):e174. doi: 10.1097/TXD.0000000000000699. eCollection 2017 Jul.
BACKGROUND
Acute rejection (AR) of kidney transplants is associated with the loss of endothelial integrity, microvascular rarefaction and, ultimately, graft dysfunction. Circulating angiogenic microRNAs (miRNAs) may serve as markers for microvascular injury. Here, we investigated the short- and long-term effects of AR after kidney transplantation on systemic vascular injury and the associated circulating miRNA profile.
METHODS
Systemic vascular injury was determined by measuring capillary tortuosity and density within the oral mucosa as well as by assessing circulating levels of angiopoietin-2/angiopoietin-1 ratio, vascular endothelial growth factor and soluble thrombomodulin. After a pilot study, we selected 48 miRNAs to assess the AR- and microvascular injury associated circulating miRNAs.
RESULTS
In stable transplant recipients (n = 25) and patients with AR (n = 13), which were also studied longitudinally (1, 6, and 12 months post-AR), we found an AR-associated increase in markers of systemic vascular injury, of which vascular endothelial growth factor and soluble thrombomodulin normalized within 1 year after AR. Of the 48 selected miRNAs, 8 were either decreased (miR-135a, miR-199a-3p, and miR-15a) or increased (miR-17, miR-140-3p, miR-130b, miR-122 and miR-192) in AR. Of these, miR-130b, miR-199a, and miR-192 associated with markers of vascular injury, whereas miR-140-3p, miR-130b, miR-122, and miR-192 normalized within 1 year after AR.
CONCLUSIONS
AR after kidney transplantation is characterized by systemic microvascular injury and associates with specific circulating miRNA levels.
背景
肾移植急性排斥反应（AR）与内皮完整性丧失、微血管稀疏以及最终的移植物功能障碍有关。循环血管生成性微小RNA（miRNA）可能作为微血管损伤的标志物。在此，我们研究了肾移植后AR对全身血管损伤的短期和长期影响以及相关的循环miRNA谱。
方法
通过测量口腔黏膜内的毛细血管迂曲度和密度以及评估血管生成素-2/血管生成素-1比值、血管内皮生长因子和可溶性血栓调节蛋白的循环水平来确定全身血管损伤。在一项初步研究之后，我们选择了48种miRNA来评估与AR和微血管损伤相关的循环miRNA。
结果
在稳定的移植受者（n = 25）和AR患者（n = 13）中，对他们也进行了纵向研究（AR后1、6和12个月），我们发现AR相关的全身血管损伤标志物增加，其中血管内皮生长因子和可溶性血栓调节蛋白在AR后1年内恢复正常。在所选的48种miRNA中，8种在AR中表达降低（miR-135a、miR-199a-3p和miR-15a）或升高（miR-17、miR-140-3p、miR-130b、miR-122和miR-192）。其中，miR-130b、miR-199a和miR-192与血管损伤标志物相关，而miR-140-3p、miR-130b、miR-122和miR-192在AR后1年内恢复正常。
结论
肾移植后的AR以全身微血管损伤为特征，并与特定的循环miRNA水平相关。
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