Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, China.
School of Pharmacy, University of Queensland, Pharmacy Australia Centre of Excellence, Woolloongabba, QLD, Australia.
Trends Pharmacol Sci. 2022 Nov;43(11):920-939. doi: 10.1016/j.tips.2022.06.009. Epub 2022 Jul 25.
Atherosclerotic cardiovascular disease (CVD), the major cause of premature human mortality, is a chronic and progressive metabolic and inflammatory disease in large- and medium-sized arteries. Mouse models are widely used to gain mechanistic insights into the pathogenesis of atherosclerosis and have facilitated the discovery of anti-atherosclerotic drugs. Despite promising preclinical studies, many drug candidates have not translated to clinical use because of the complexity of disease patho-mechanisms including lipid metabolic traits and inflammatory, genetic, and hemodynamic factors. We review the current preclinical utility and translation potential of traditional [apolipoprotein E (APOE)- and low-density lipoprotein (LDL) receptor (LDLR)-deficient mice] and emerging mouse models that include partial carotid ligation and AAV8-Pcsk9-D377Y injection in atherosclerosis research and drug discovery. This article represents an important resource in atherosclerosis research.
动脉粥样硬化性心血管疾病(CVD)是人类过早死亡的主要原因,它是一种发生在大中动脉的慢性、进行性代谢和炎症性疾病。小鼠模型被广泛用于深入了解动脉粥样硬化的发病机制,并促进了抗动脉粥样硬化药物的发现。尽管有许多有前景的临床前研究,但由于疾病病理机制的复杂性,包括脂质代谢特征和炎症、遗传和血液动力学因素,许多药物候选物未能转化为临床应用。我们综述了传统的[载脂蛋白 E(APOE)和低密度脂蛋白受体(LDLR)缺陷小鼠]和新兴的小鼠模型在动脉粥样硬化研究和药物发现中的当前临床前应用和转化潜力,这些模型包括颈动脉部分结扎和 AAV8-Pcsk9-D377Y 注射。本文是动脉粥样硬化研究中的一个重要资源。