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.

IF 5.6 1区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Regenerative Biomaterials Pub Date : 2024-08-06 eCollection Date: 2024-01-01 DOI:10.1093/rb/rbae089
Sainan Liu, Jinquan Huang, Jiayan Luo, Qihao Bian, Yajun Weng, Li Li, Junying Chen
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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.

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基于材料生物学视野的肝 X 受体激动剂治疗生物材料,可在原位调节动脉粥样硬化斑块的消退,用于设备表面工程。
经皮冠状动脉介入治疗是冠状动脉粥样硬化的主要治疗方法。目前,大多数研究侧重于血液成分和平滑肌细胞,以达到抗凝或抗增殖的效果,而材料对巨噬细胞的介导作用也是关注的焦点。富含高胆固醇的巨噬细胞泡沫是动脉粥样硬化斑块的一个显著特征。激活肝脏 X 受体(LXR)以调节胆固醇外流和排泄,减少斑块中巨噬细胞泡沫细胞的数量,对于动脉粥样硬化的消退是可行的。然而,促进胆固醇外流仍局限于靶向疗法。本文将 LXR 激动剂(GW3965)引入材料表面并原位递送至动脉粥样硬化巨噬细胞,以提高抗动脉粥样硬化治疗和斑块消退的药物利用率。LXR 激动剂通过多通道调节巨噬细胞,包括脂质代谢(ABCA1、ABCG1 和低密度脂蛋白受体)、巨噬细胞迁移(CCR7)和排泄(MerTK),起到抑制斑块的作用。装载了 LXR 激动剂的材料明显减轻了动脉粥样硬化模型大鼠的斑块负担,最重要的是,它不会引起肝毒性以及材料植入后的再狭窄和血栓形成等不良反应。体内和体外评估均证实了其抗动脉粥样硬化的能力和安全性。总之,具有病理微环境调节作用的多功能 LXR 激动剂负载材料有望成为抗动脉粥样硬化的候选材料,并有可能应用于心血管设备表面工程。
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来源期刊
Regenerative Biomaterials
Regenerative Biomaterials Materials Science-Biomaterials
CiteScore
7.90
自引率
16.40%
发文量
92
审稿时长
10 weeks
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.
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