动脉粥样硬化的非啮齿动物模型:现有药物的再利用和新型治疗策略的探索。

IF 2.4 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Siarhei A Dabravolski, Victoria A Khotina, Mikhail A Popov, Victor Y Glanz, Vasily N Sukhorukov, Alexander N Orekhov
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引用次数: 0

摘要

动脉粥样硬化和相关的心血管疾病是全球疾病和死亡的主要原因。动脉粥样硬化的发展是一个复杂的过程,涉及氧化应激、过剩脂质沉积和滞留、内皮功能障碍和慢性炎症。开发新的抗动脉粥样硬化药物和对现有药物进行再利用需要使用合适的动物模型来描述动脉粥样硬化发生和发展的基本机制,并评估潜在的治疗效果。然而,常用的啮齿类动物模型并不总是合适的,可能需要其他模型才能将这些发现转化为有价值的预防和治疗药物供人类应用。最近在大型动物基因编辑工具方面取得的进展使我们能够制造出在病变定位和组织病理学方面发展得更快、与人类更相似的动脉粥样硬化动物。在这篇综述中,我们将讨论主要非啮齿类动物动脉粥样硬化动物模型的主要优点和缺点,特别是兔子、猪、斑马鱼和非人灵长类动物。此外,我们还回顾了最近发明的新型治疗方法和药物,以及现有药物(如抗糖尿病和抗癌药)在动脉粥样硬化治疗中的再利用,其疗效已在非啮齿动物动脉粥样硬化动物模型上得到验证。总之,正确选择合适的动脉粥样硬化动物模型有助于在现有药物的再利用、发现新的治疗策略和验证新型抗动脉粥样硬化药物方面开展可重复的、严谨的转化研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Non-rodent Models of Atherosclerosis: Repurposing of Existing Drugs and Search for Novel Treatment Strategies.

Atherosclerosis and associated cardiovascular diseases are the leading causes of illness and mortality worldwide. The development of atherosclerosis is a complex process involving oxidative stress, surplus lipid deposition and retention, endothelial dysfunction, and chronic inflammation. Developing novel anti-atherogenic and repurposing existing drugs requires the use of suitable animal models to characterise the fundamental mechanisms underlying atherosclerosis initiation and progression and to evaluate potential therapeutic effects. Commonly used rodent models, however, are not always appropriate, and other models may be required to translate these discoveries into valuable preventive and treatment agents for human applications. Recent advances in gene-editing tools for large animals have allowed the creation of animals that develop atherosclerosis faster and more similarly to humans in terms of lesion localisation and histopathology. In this review, we discuss the major advantages and drawbacks of the main non-rodent animal models of atherosclerosis, particularly rabbits, pigs, zebrafish, and non-human primates. Moreover, we review the application of recently invented novel therapeutic methods and agents, and repurposed existing drugs (such as antidiabetic and anticancer) for atherosclerosis treatment, the efficacy of which is verified on non-rodent animal models of atherosclerosis. In total, the proper selection of a suitable animal model of atherosclerosis facilitates reproducible and rigorous translational research in repurposing of existing drugs, discovering new therapeutic strategies, and validating novel anti-atherosclerotic drugs.

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来源期刊
Current Cardiology Reviews
Current Cardiology Reviews CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
3.70
自引率
10.50%
发文量
117
期刊介绍: Current Cardiology Reviews publishes frontier reviews of high quality on all the latest advances on the practical and clinical approach to the diagnosis and treatment of cardiovascular disease. All relevant areas are covered by the journal including arrhythmia, congestive heart failure, cardiomyopathy, congenital heart disease, drugs, methodology, pacing, and preventive cardiology. The journal is essential reading for all researchers and clinicians in cardiology.
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