AUTHOR=Jiang Siyu , Ai Yingjie , Ni Liyuan , Wu Ling , Huang Xiaoquan , Chen Shiyao TITLE=Platelet-derived TGF-β1 is related to portal vein thrombosis in cirrhosis by promoting hypercoagulability and endothelial dysfunction JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.938397 DOI=10.3389/fcvm.2022.938397 ISSN=2297-055X ABSTRACT=Background

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.

Materials and methods

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.

Results

Our results uncovered that TGF-β1 (6,866.55 vs. 3,840.60 pg/ml, P = 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; P < 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.

Conclusion

Elevated platelet-derived TGF-β1 exhibited association with hypercoagulability and promoting effect on endothelial dysfunction, closely related with PVT in cirrhotic patients.