Zebrafish models of cardiovascular disease
Zebrafish models of cardiovascular disease
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DOI：
10.1007/s10741-016-9579-y
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发表时间：
2016-11-01
影响因子：
4.6
通讯作者：
Beis, Dimitris
中科院分区：
文献类型：
--
作者：
Bournele, Despina;Beis, Dimitris
心血管疾病（CVD）是全球主要的死亡原因之一。与心脏病发展相关的最重要的风险因素包括遗传和环境因素，如高血压、高血胆固醇水平、糖尿病、吸烟和肥胖。冠状动脉疾病占心血管疾病死亡的最高百分比，其次是中风、心肌病、先天性心脏病、心脏瓣膜缺陷和心律失常。所有形式的心血管疾病的原因，预防和治疗仍然是生物医学研究的活跃领域，每周发表数百项科学研究。建立心血管疾病的动物模型是了解发病机制以及设计和测试新疗法的主要方法。在这里，我们将重点介绍最近的进展，以寻找心血管疾病的遗传原因和分子机制，以及新的药物来治疗他们，使用一种小型的热带淡水鱼原产于东南亚：斑马鱼（Danio rerio）。斑马鱼作为一种高通量但低成本的模式生物出现，它结合了正向和反向遗传学与表型驱动的药物筛选的优势。非侵入性成像允许在体内分析心血管表型。来自全基因组关联研究的候选基因的功能验证已经证实了几个基因在CVD的病理生理学中的作用。此外，斑马鱼心脏在其一生中保持再生能力，为了解人类心脏再生提供了新的见解。
Cardiovascular disease (CVD) is one of the leading causes of death worldwide. The most significant risk factors associated with the development of heart diseases include genetic and environmental factors such as hypertension, high blood cholesterol levels, diabetes, smoking, and obesity. Coronary artery disease accounts for the highest percentage of CVD deaths and stroke, cardiomyopathies, congenital heart diseases, heart valve defects and arrhythmias follow. The causes, prevention, and treatment of all forms of cardiovascular disease remain active fields of biomedical research, with hundreds of scientific studies published on a weekly basis. Generating animal models of cardiovascular diseases is the main approach used to understand the mechanism of pathogenesis and also design and test novel therapies. Here, we will focus on recent advances to finding the genetic cause and the molecular mechanisms of CVDs as well as novel drugs to treat them, using a small tropical freshwater fish native to Southeast Asia: the zebrafish (Danio rerio). Zebrafish emerged as a high-throughput but low-cost model organism that combines the advantages of forward and reverse genetics with phenotype-driven drug screenings. Noninvasive imaging allows in vivo analyses of cardiovascular phenotypes. Functional verification of candidate genes from genome-wide association studies has verified the role of several genes in the pathophysiology of CVDs. Also, zebrafish hearts maintain their ability to regenerate throughout their lifetime, providing novel insights to understand human cardiac regeneration.