Crassostrea gigas-Based Bioactive Peptide Protected Thrombin-Treated Endothelial Cells against Thrombosis and Cell Barrier Dysfunction

Journal of Agricultural and Food Chemistry, vol. 70, pp. 9664–9673

Abstract

The activation of thrombin-treated endothelial cells resulted in disruption of the vascular tissues. A novel oyster-derived bioactive dodecapeptide (IEELEELEAER, P-2-CG) was reported to protect the human umbilical vein endothelial cells and their barrier function via the decrease of VE-cadherin disruption and the restoration of the F-actin arrangement. The promotion of the extrinsic pathway in this case triggers the release of tissue factors that occurs on the surface of the endothelial cells, thus changing the antithrombotic to prothrombotic. P-2-CG induced accordingly a prolongation of plasma clotting time and thrombin generation time, following the alteration of the antithrombotic phenotype. Furthermore, the antithrombotic activity of P-2-CG was also supported by the reduction of FXa and the inhibition of other factors release, for instance, inflammation factors, ROS, etc. In addition to its antithrombogenic role, P-2-CG displayed anti-inflammatory and antioxidant properties via the mitogen-activated protein kinase cascades and central signaling pathways as shown in an in vitro model of endothelial dysfunction.

Authors 6

1. Shuzhen Cheng Aachen Division of Thrombosis and Hemostasis Einthoven Laboratory for Vascular and Regenerative Medicine

   Leiden University · Leiden University Medical Center · Dalian Polytechnic University

   Affiliation as printed

   Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands

   School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China

2. Di Wu

   Dalian Polytechnic University

   Affiliation as printed

   School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China

3. Lushun Yuan Aachen Einthoven Laboratory for Vascular and Regenerative Medicine Department of Internal Medicine

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   The Einthoven Laboratory for Vascular and Regenerative Medicine, Department of Internal Medicine, Nephrology, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands

4. Hanxiong Liu

   Dalian Polytechnic University

   Affiliation as printed

   School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China

5. Hesham R. EI‐Seedi

   Uppsala University

   Affiliation as printed

   Pharmacognosy Group, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Uppsala 75123, Sweden

6. Ming Du corresponding

   Dalian Polytechnic University

   Affiliation as printed

   School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China