LOX‐1‐Based Assembly Layer on Devices Surface to Promote Endothelial Repair and Reduce Complications for In Situ Interventional Plaque

Poly I-modified material can effectively resist the endothelial damage caused by oxidative stress, promote the adhesion and proliferation of EC, reduce the production of ROS and inflammatory reaction, restore mitochondrial membrane potential, and promote rapid endothelialization on the surface of the material. Additionally, Poly I modifications can also inhibit cholesterol uptake and regulate macrophage transformation into anti-inflammatory M2 phenotype.

Abstract

Rapid endothelialization and functional recovery are considered as promising methods to extend the long-term effectiveness of cardiovascular implant materials. LOX-1 participates in the initiation and development of atherosclerosis and is highly expressed in a variety of cells involved in atherosclerosis, hence it is feasible to accelerate the recovery of endothelial function and inhibit the development of existing plaques by regulating LOX-1. Herein, the surface is modified with Poly I, a LOX-1 inhibitor, using rich amino dendritic macromolecules (PAMAM) as the linker coating, to against the pathological microenvironment. Poly I modified surface resisted endothelial damage caused by oxidative stress through the LOX-1-NADPH signaling pathway and inhibited endothelial inflammation via the LOX-1-NF-κB signaling pathway. It also promoted endothelial cell migration and inhibited platelet adhesion. Moreover, the Poly I modified surface can inhibit oxLDL-induced macrophage foam cell formation and alleviate inflammation by modulating macrophage phenotypes. Poly I modified surface significantly reduced plaque burden after treatment of atherosclerotic model rats, most importantly, it significantly inhibited post-implantation-induced restenosis and thrombosis. In vivo and in vitro evaluations confirmed its safety and therapeutic efficacy against atherosclerosis. Overall, the multifunctional Poly I with pathological microenvironment regulation exhibits potential application value in the surface engineering of cardiovascular devices.