Department of Medicine, University of California, San Diego, La Jolla, Calif.
Department of Medicine, University of California, San Diego, La Jolla, Calif.
Transl Res. 2014 Feb;163(2):99-108. doi: 10.1016/j.trsl.2013.09.004. Epub 2013 Oct 2.
Lipid and lipoprotein metabolism in zebrafish and in humans are remarkably similar. Zebrafish express all major nuclear receptors, lipid transporters, apolipoproteins and enzymes involved in lipoprotein metabolism. Unlike mice, zebrafish express cetp and the Cetp activity is detected in zebrafish plasma. Feeding zebrafish a high cholesterol diet, without any genetic intervention, results in significant hypercholesterolemia and robust lipoprotein oxidation, making zebrafish an attractive animal model to study mechanisms relevant to early development of human atherosclerosis. These studies are facilitated by the optical transparency of zebrafish larvae and the availability of transgenic zebrafish expressing fluorescent proteins in endothelial cells and macrophages. Thus, vascular processes can be monitored in live animals. In this review article, we discuss recent advances in using dyslipidemic zebrafish in atherosclerosis-related studies. We also summarize recent work connecting lipid metabolism with regulation of angiogenesis, the work that considerably benefited from using the zebrafish model. These studies uncovered the role of aibp, abca1, abcg1, mtp, apoB, and apoC2 in regulation of angiogenesis in zebrafish and paved the way for future studies in mammals, which may suggest new therapeutic approaches to modulation of excessive or diminished angiogenesis contributing to the pathogenesis of human disease.
斑马鱼和人类的脂类和脂蛋白代谢非常相似。斑马鱼表达所有主要的核受体、脂质转运蛋白、载脂蛋白和参与脂蛋白代谢的酶。与小鼠不同，斑马鱼表达 CETP，并且在斑马鱼血浆中检测到 CETP 活性。用高胆固醇饮食喂养斑马鱼，无需任何基因干预，就会导致显著的高胆固醇血症和强烈的脂蛋白氧化，使斑马鱼成为研究与人类动脉粥样硬化早期发展相关机制的有吸引力的动物模型。这些研究得益于斑马鱼幼虫的光学透明度和表达荧光蛋白的转基因斑马鱼在血管内皮细胞和巨噬细胞中的可用性。因此，可以在活体动物中监测血管过程。在这篇综述文章中，我们讨论了利用血脂异常斑马鱼进行动脉粥样硬化相关研究的最新进展。我们还总结了最近将脂质代谢与血管生成调节联系起来的工作，这项工作得益于使用斑马鱼模型。这些研究揭示了 AIBP、ABCA1、ABCG1、MTp、apoB 和 apoC2 在斑马鱼血管生成调节中的作用，为未来在哺乳动物中的研究铺平了道路，这可能为调节导致人类疾病发病机制的过度或不足的血管生成提供新的治疗方法。
