Lü Ping, Jiao Qibin, Shimura Daisuke, Kusakari Yoichiro, Liu Fang, Minamisawa Susumu
Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Institute of Ageing Research, School of Medicine, Hangzhou Normal University, Hangzhou, China.
Ann Vasc Surg. 2018 May;49:168-178. doi: 10.1016/j.avsg.2017.12.011. Epub 2018 Mar 1.
Previous research has revealed that patent vein grafts lose their venous identity Eph-B4 but do not gain arterial identity ephrin-B2 during adaptation to the arterial circulation, and vascular identity marker, for example, the Eph-B4 signaling is a critical determinant of venous wall thickness of vein grafts. But what is the remodeling pattern, especially the remodeling pattern of vascular identity in the venous segment of arteriovenous shunt at a late stage postoperation has not been fully explored. This study was conducted to characterize the remodeling pattern of shear stress, vascular identity, structural composition and morphology, and transcriptional profiles in jugular segment of carotid-jugular (CJ) shunt and/or pulmonary artery (PA), which delivers an increased amount of mixed blood at a late stage postoperation in adult rats.
CJ shunt was created in adult Wistar rats via end-to-end anastomosis of carotid artery (CA) and jugular vein (JV). At the time of 15 weeks, after hemodynamics test, remodeled jugular segment of CJ shunt, PA, and sham-operated corresponding vessels were isolated. Reverse transcription polymerase chain reaction, microarray, western blot, immunohistochemistry experiments, and morphology analyses were performed.
CJ shunt shear stresses have been patterned to some sort of balance with no significant difference in shear stress between carotid segment and jugular segment (P > 0.05). Immunohistochemical analysis reveals that venous identity marker Eph-B4 is lost, but arterial identity markers ephrin-B2 and regulator of G-protein signaling 5 are gained in jugular segment of CJ shunt (P < 0.01), and these 2 arterial identity markers further strengthened in PA (P < 0.01) in shunted rats compared with controls. Jugular segment of CJ shunt undergoes significant intimal hyperplasia with strong expression of smooth muscle cell markers (P < 0.05) and demonstrates a distinct transcriptional profiles which reveals that transcripts of 5 arterial markers are significantly upregulated (P < 0.05 or < 0.01) compared with sham-operated JV; among them, G-protein signaling 5 is exactly the gene with the largest fold change (10.14-fold) in all genes tested by microarray experiment.
Venous identity is lost, but arterial identity is gained in jugular segment of CJ shunt and arterial identity further strengthened in PA in adult shunted rats during late adaptation.
先前的研究表明，在适应动脉循环的过程中，静脉移植血管失去其静脉标志物Eph-B4，但并未获得动脉标志物ephrin-B2，并且血管标志物，例如Eph-B4信号传导是静脉移植血管静脉壁厚度的关键决定因素。但是，在术后晚期动静脉分流的静脉段中，尤其是血管标志物的重塑模式尚未得到充分研究。本研究旨在描述成年大鼠术后晚期颈静脉-颈动脉（CJ）分流和/或肺动脉（PA）中颈静脉段的剪切应力、血管标志物、结构组成和形态以及转录谱的重塑模式，这些部位在术后晚期输送增加量的混合血液。
通过颈动脉（CA）和颈静脉（JV）的端端吻合在成年Wistar大鼠中创建CJ分流。在15周时，在进行血流动力学测试后，分离出CJ分流、PA和假手术对照血管的重塑颈静脉段。进行逆转录聚合酶链反应、微阵列、蛋白质印迹、免疫组织化学实验和形态学分析。
CJ分流的剪切应力已形成某种平衡，颈动脉段和颈静脉段之间的剪切应力无显著差异（P>0.05）。免疫组织化学分析显示，CJ分流颈静脉段中静脉标志物Eph-B4丢失，但获得了动脉标志物ephrin-B2和G蛋白信号调节因子5（P<0.01），与对照组相比，这些动脉标志物在分流大鼠的PA中进一步增强（P<0.01）。CJ分流的颈静脉段发生显著的内膜增生，平滑肌细胞标志物表达强烈（P<0.05），并表现出独特的转录谱，显示与假手术的颈静脉相比，5种动脉标志物的转录本显著上调（P<0.05或<0.01）；其中，G蛋白信号调节因子5正是在微阵列实验测试的所有基因中变化倍数最大（10.14倍）的基因。
在成年分流大鼠的晚期适应过程中，CJ分流的颈静脉段失去静脉标志物，但获得动脉标志物，并且动脉标志物在PA中进一步增强。
