Endothelium-Mimetic Surface Modification Improves Antithrombogenicity and Enhances Patency of Vascular Grafts in Rats and Pigs

Yongzhen Wei; Huan Jiang; Chao Chai; Pei Liu; Meng Qian; Na Sun; Man Gao; Honglin Zu; Yongquan Yu; Guangbo Ji; Yating Zhang; Sen Yang; Ju He; Jiansong Cheng; Jinwei Tian; Qiang Zhao

doi:10.1016/j.jacbts.2022.12.009

Endothelium-Mimetic Surface Modification Improves Antithrombogenicity and Enhances Patency of Vascular Grafts in Rats and Pigs

JACC Basic Transl Sci. 2023 May 3;8(7):843-861. doi: 10.1016/j.jacbts.2022.12.009. eCollection 2023 Jul.

Authors

Yongzhen Wei^{1

2}, Huan Jiang², Chao Chai³, Pei Liu², Meng Qian², Na Sun⁴, Man Gao¹, Honglin Zu⁵, Yongquan Yu⁶, Guangbo Ji², Yating Zhang², Sen Yang⁵, Ju He⁵, Jiansong Cheng¹, Jinwei Tian⁴, Qiang Zhao²

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, China.
² State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials (Ministry of Education), Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, China.
³ Department of Radiology, Tianjin Institute of Imaging Medicine, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
⁴ Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Key Laboratory of Myocardial Ischemia (Ministry of Education), Harbin, China.
⁵ Department of Vascular Surgery, Tianjin First Central Hospital, Nankai University, Tianjin, China.
⁶ Department of Radiology, Weihai Central Hospital, Weihai, China.

Abstract

We first identified thrombomodulin (TM) and endothelial nitric oxide (NO) synthase as key factors for the antithrombogenic function of the endothelium in human atherosclerotic carotid arteries. Then, recombinant TM and an engineered galactosidase responsible for the conversion of an exogenous NO prodrug were immobilized on the surface of the vascular grafts. Surface modification by TM and NO cooperatively enhanced the antithrombogenicity and patency of vascular grafts. Importantly, we found that the combination of TM and NO also promoted endothelialization, whereas it reduced adverse intimal hyperplasia, which is critical for the maintenance of vascular homeostasis, as confirmed in rat and pig models.

Keywords: antithrombogenic surface modification; endothelialization; nitric oxide; thrombomodulin; vascular grafts.