摘要
尽管许多的治疗在发展,动脉粥样硬化和它的并发症仍是全世界主要的致死原因。动脉粥样硬化是一种复杂的,多级的疾病通过脂质代谢导致胆固醇在血管内积累和空斑形成。制造动脉粥样硬化小鼠模型来研究具体分子运动机制。我们这里牵涉动脉粥样硬化的非脂质体受体来揭露在前面所提及小鼠模型的它们总的或者具体的消除。受体评估跨度范围广泛,从与脂代谢相关(脂连蛋白受体)的分子到与分子的动脉粥样硬化连接是不太明显的(大麻素受体)分子。我们还概述横移植研究这使得从那些抗炎效果得出解偶联脂质调制。对于某些受体,由于击倒是无法获得的,所以药理学数据列来代替。我们强调受体的病理学贡献,基于功能性标准,例如氧化应激,免疫应答,炎症,血管生成。对于一些受体的亲和和抵抗动脉粥样硬化的活动有争议的方面突出显示。我们假定这些差异是由于在实验装置,动物模型使用,组织特异性作用,分析了各种异构体,发散信令或代谢和免疫途径之间的串扰。了解细胞受体的影响在动脉粥样硬化的进展,使得它们调制抗动脉粥样的表型。实验研究的动物模型是在某些情况下,成功地外推到人类导致动脉粥样硬化减少,我们预计随着基础上的最新成果出现,甚至程度将更大。
关键词: 动脉粥样硬化,膜受体,小鼠模型,动脉粥样硬化斑块,内皮功能紊乱,巨噬细胞,血管平滑肌细胞
Current Molecular Medicine
Title:Beyond Lipoprotein Receptors: Learning from Receptor Knockouts Mouse Models about New Targets for Reduction of the Atherosclerotic Plaque.
Volume: 15 Issue: 10
Author(s): V. G. Trusca, E. V. Fuior and A. V. Gafencu
Affiliation:
关键词: 动脉粥样硬化,膜受体,小鼠模型,动脉粥样硬化斑块,内皮功能紊乱,巨噬细胞,血管平滑肌细胞
摘要: Atherosclerosis and its complications represent the leading death cause worldwide, despite many therapeutic developments. Atherosclerosis is a complex, multistage disease whereby perturbed lipid metabolism leads to cholesterol accumulation into the vascular walls and plaque formation. Generation of apoE-/- and LDLR-/- atherosclerosis mouse models opened the avenue for investigating the mechanisms of action for specific molecules. We focus herein on the involvement of non-lipoprotein receptors in atherogenesis, as revealed by their total or site-specific ablation in the aforementioned murine models. The receptors reviewed span a broad range, from molecules related to lipid metabolism (adiponectin receptors) to molecules whose connection with atherogenesis is less obvious (cannabinoid receptors). We also outline cross-transplantation studies which allowed uncoupling the lipid modulating effects from the inflammatory ones. For certain receptors, since knockouts were unavailable, pharmacological data are presented instead. We emphasize the contribution of the receptors to the pathology, based on functional criteria, such as oxidative stress, immune response, inflammation, angiogenesis. Controversial aspects regarding the pro- or anti- atherogenic activity of some receptors are highlighted. We assume these discrepancies are due to the experimental setup, animal models used, tissue-specific action, various isoforms analyzed, divergent signaling or cross-talk between metabolic and immune pathways. Understanding the influences of cellular receptors in the progression of atherosclerosis allows their modulation towards an antiatherogenic phenotype. The experimental studies in animal models were in some cases successfully extrapolated to humans leading to atheroma reduction, and we expect this to occur even to a greater extent, based on the newest achievements.
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V. G. Trusca, E. V. Fuior and A. V. Gafencu , Beyond Lipoprotein Receptors: Learning from Receptor Knockouts Mouse Models about New Targets for Reduction of the Atherosclerotic Plaque., Current Molecular Medicine 2015; 15 (10) . https://dx.doi.org/10.2174/1566524016666151123110310
DOI https://dx.doi.org/10.2174/1566524016666151123110310 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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