Schlegel Amnon
University of Utah Molecular Medicine Program, School of Medicine, University of Utah, Salt Lake City, UT, USA; Department of Internal Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Utah, Salt Lake City, UT, USA; Department of Biochemistry, School of Medicine, University of Utah, Salt Lake City, UT, USA; Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA.
Front Endocrinol (Lausanne). 2016 Dec 16;7:159. doi: 10.3389/fendo.2016.00159. eCollection 2016.
Atherosclerotic cardiovascular disease is the leading cause of death. Elevated circulating concentrations of lipids are a central pathogenetic driver of atherosclerosis. While numerous effective therapies for this condition have been developed, there is substantial unmet need for this pandemic illness. Here, I will review nutritional, physiological, genetic, and pathological discoveries in the emerging zebrafish model for studying dyslipidemia and atherosclerosis. The technical and physiological advantages and the pharmacological potential of this organism for discovery and validation of dyslipidemia and atherosclerosis targets are stressed through summary of recent findings. An emerging literature shows that zebrafish, through retention of a ortholog gene and high sensitivity to ingestion of excess cholesterol, rapidly develops hypercholesterolemia, with a pattern of distribution of lipid species in lipoprotein particles similar to humans. Furthermore, recent studies leveraging the optical transparency of zebrafish larvae to monitor the fate of these ingested lipids have provided exciting insights to the development of dyslipidemia and atherosclerosis. Future directions for investigation are considered, with particular attention to the potential for cell biological study of atherosclerotic plaques.
动脉粥样硬化性心血管疾病是主要的死亡原因。循环脂质浓度升高是动脉粥样硬化的核心致病驱动因素。虽然已经开发出许多针对这种疾病的有效疗法，但对于这种大流行疾病仍有大量未满足的需求。在这里，我将回顾新兴的斑马鱼模型在研究血脂异常和动脉粥样硬化方面的营养、生理、遗传和病理学发现。通过总结近期研究结果，强调了这种生物体在发现和验证血脂异常和动脉粥样硬化靶点方面的技术和生理优势以及药理学潜力。新兴文献表明，斑马鱼通过保留直系同源基因以及对摄入过量胆固醇高度敏感，会迅速发展为高胆固醇血症，其脂蛋白颗粒中的脂质种类分布模式与人类相似。此外，最近利用斑马鱼幼体的光学透明度来监测这些摄入脂质的命运的研究，为血脂异常和动脉粥样硬化的发展提供了令人兴奋的见解。我们考虑了未来的研究方向，特别关注动脉粥样硬化斑块细胞生物学研究的潜力。
