Therapeutic biomaterials with liver X receptor agonists based on the horizon of material biology to regulate atherosclerotic plaque regression in situ for devices surface engineering.
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引用次数: 0
Abstract
Percutaneous coronary interventional is the main treatment for coronary atherosclerosis. At present, most studies focus on blood components and smooth muscle cells to achieve anticoagulation or anti-proliferation effects, while the mediated effects of materials on macrophages are also the focus of attention. Macrophage foam cells loaded with elevated cholesterol is a prominent feature of atherosclerotic plaque. Activation of liver X receptor (LXR) to regulate cholesterol efflux and efferocytosis and reduce the number of macrophage foam cells in plaque is feasible for the regression of atherosclerosis. However, cholesterol efflux promotion remains confined to targeted therapies. Herein, LXR agonists (GW3965) were introduced on the surface of the material and delivered in situ to atherogenic macrophages to improve drug utilization for anti-atherogenic therapy and plaque regression. LXR agonists act as plaque inhibition mediated by multichannel regulation macrophages, including lipid metabolism (ABCA1, ABCG1 and low-density lipoprotein receptor), macrophage migration (CCR7) and efferocytosis (MerTK). Material loaded with LXR agonists significantly reduced plaque burden in atherosclerotic model rats, most importantly, it did not cause hepatotoxicity and adverse reactions such as restenosis and thrombosis after material implantation. Both in vivo and in vitro evaluations confirmed its anti-atherosclerotic capability and safety. Overall, multi-functional LXR agonist-loaded materials with pathological microenvironment regulation effect are expected to be promising candidates for anti-atherosclerosis and have potential applications in cardiovascular devices surface engineering.
期刊介绍:
Regenerative Biomaterials is an international, interdisciplinary, peer-reviewed journal publishing the latest advances in biomaterials and regenerative medicine. The journal provides a forum for the publication of original research papers, reviews, clinical case reports, and commentaries on the topics relevant to the development of advanced regenerative biomaterials concerning novel regenerative technologies and therapeutic approaches for the regeneration and repair of damaged tissues and organs. The interactions of biomaterials with cells and tissue, especially with stem cells, will be of particular focus.