Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice.

IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY
Muxin Yu, Chuwei Zheng, Xiaoguang Wang, Rong Peng, Guoming Lu, Jinming Zhang
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引用次数: 0

Abstract

Introduction: Hypercoagulability contributes to the majority of deaths and organ failure associated with obstructive jaundice (OJ). However, the exact mechanism of the coagulopathy in OJ remains elusive. Our objectives were to demonstrate whether phosphatidylserine (PS) exposure on blood cells (BCs), microparticles (MPs), and endothelial cells (ECs) can account for the hypercoagulability and liver damage in OJ patients.

Methods: We evaluated OJ patients at two time point, which before (Day 0) and 7 days (Day 7) after the endoscopic retrograde cholangiopancreatography procedure (ERCP), and compared with healthy controls. Lactadherin was used to quantify PS exposure on BCs, MPs and ECs. Human umbilical vein endothelial cells (HUVECs) were incubated with serum of OJ patients and the expression of PS were evaluated. Meanwhile, healthy BCs and HUVECs were treated with 0, 25, 50 or 100µM unconjugated bilirubin (UCB) and PS exposure on cells were evaluated. Procoagulant activity was evaluated by purified coagulation complex assays, clotting time, and fibrin turbidity. In addition, we established a cholestatic mouse model by bile duct ligation to determine the potential role of PS in intrahepatic coagulation and liver damage.

Results: Using flow cytometry, we found that OJ patients exhibited elevated levels of PS + BCs and associated MPs compared to the controls. Furthermore, the number of PS + BCs and MPs in patients at Day 0 were significantly higher than in patients at Day 7. Similarly, we observed markedly elevated PS exposure on HUVECs cultured with serum from patients at Day 0 versus serum from patients at Day 7. In vitro assays, PS exposure on BCs and HUVECs progressively increased with the concentration of UCB. Moreover, PS + BCs and MPs contributed to greatly shortened coagulation time and markedly enhanced coagulation factor Xa, thrombin, and fibrin generation. This procoagulant activity could be blocked approximately 80%, by the addition of lactadherin. Moreover, cholestatic mice exhibited significantly increased levels of liver tissue necrosis, fibrin deposition, and thrombophilia compared to sham mice. The enhanced intrahepatic coagulation and liver injury could be reversed by inhibiting PS with lactadherin.

Conclusions: These results highlight the pathogenic activity of PS + cells and MPs in promoting a prothrombotic environment and liver damage in OJ. As such, lactadherin, a PS blockade, may be a viable therapeutic strategy for treating such patients.

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来源期刊
BMC Gastroenterology
BMC Gastroenterology 医学-胃肠肝病学
CiteScore
4.20
自引率
0.00%
发文量
465
审稿时长
6 months
期刊介绍: BMC Gastroenterology is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of gastrointestinal and hepatobiliary disorders, as well as related molecular genetics, pathophysiology, and epidemiology.
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