Jiang Siyu, Ai Yingjie, Ni Liyuan, Wu Ling, Huang Xiaoquan, Chen Shiyao
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.
Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital of Fudan University, Shanghai, China.
Front Cardiovasc Med. 2022 Sep 26;9:938397. doi: 10.3389/fcvm.2022.938397. eCollection 2022.
Portal vein thrombosis (PVT) is a serious complication of cirrhosis accompanied by unclear pathogenesis. Transforming growth factor-beta (TGF-β) has been implicated in atherosclerosis and venous thrombosis whereas study regarding its part in PVT is lacking. The aim of this study was to explore the role of cytokine TGF-β1 in PVT and the potential mechanism.
We included patients with cirrhotic gastroesophageal varices and divided them into two groups according to the presence of PVT. Serum levels of TGF-β1 were detected using Cytometric Bead Array kit and compared between two groups. Coagulation status was assessed using thromboelastography (TEG). Primary liver sinusoidal endothelial cells were treated with TGF-β1 and evaluated for endothelial dysfunction by RT-PCR.
Our results uncovered that TGF-β1 (6,866.55 vs. 3,840.60 pg/ml, = 0.015) significantly increased in the PVT group. Splenectomy might promote PVT by increasing platelet-derived TGF-β1 levels. Other cytokines showed no difference between PVT and non-PVT groups. Besides, TGF-β1 was correlated with platelet, fibrinogen, TEG-CI, TEG-MA, and TEG-α (coef = 0.733, 0.494, 0.604, 0.608, and 0.511; < 0.001, 0.027, 0.004, 0.004, and 0.021, respectively), which indicated a hypercoagulable state in PVT patients. RT-PCR of liver sinusoidal endothelial cells showed a markable increment of von Willebrand Factor (vWF), thrombomodulin(TM), intercellular adhesion moleclar-1(ICAM-1), and vascular endothelial growth factor(VEGF) after TGF-β1 treatment, suggesting the involvement of endothelial dysfunction.
Elevated platelet-derived TGF-β1 exhibited association with hypercoagulability and promoting effect on endothelial dysfunction, closely related with PVT in cirrhotic patients.
门静脉血栓形成（PVT）是肝硬化的一种严重并发症，其发病机制尚不清楚。转化生长因子-β（TGF-β）与动脉粥样硬化和静脉血栓形成有关，而关于其在PVT中的作用的研究尚缺乏。本研究的目的是探讨细胞因子TGF-β1在PVT中的作用及潜在机制。
我们纳入了肝硬化食管胃静脉曲张患者，并根据是否存在PVT将他们分为两组。使用细胞计数珠阵列试剂盒检测血清TGF-β1水平，并在两组之间进行比较。使用血栓弹力图（TEG）评估凝血状态。用TGF-β1处理原代肝窦内皮细胞，并通过RT-PCR评估内皮功能障碍。
我们的结果发现，PVT组中TGF-β1（6,866.55对3,840.60 pg/ml，P = 0.015）显著升高。脾切除术可能通过增加血小板衍生的TGF-β1水平来促进PVT。其他细胞因子在PVT组和非PVT组之间没有差异。此外，TGF-β1与血小板、纤维蛋白原、TEG-CI、TEG-MA和TEG-α相关（系数分别为0.733、0.494、0.604、0.608和0.511；P分别<0.001、0.027、0.004、0.004和0.021），这表明PVT患者存在高凝状态。肝窦内皮细胞的RT-PCR显示，TGF-β1处理后血管性血友病因子（vWF）、血栓调节蛋白（TM）、细胞间粘附分子-1（ICAM-1）和血管内皮生长因子（VEGF）显著增加，提示内皮功能障碍的参与。
血小板衍生的TGF-β1升高与高凝状态相关，并对内皮功能障碍有促进作用，与肝硬化患者的PVT密切相关。
