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心血管疾病的斑马鱼模型。

Zebrafish models of cardiovascular disease.

作者信息

Bournele Despina, Beis Dimitris

机构信息

Zebrafish Disease Models Lab, Center for Clinical Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, Athens, Greece.

Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

出版信息

Heart Fail Rev. 2016 Nov;21(6):803-813. doi: 10.1007/s10741-016-9579-y.

Abstract

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.

摘要

心血管疾病(CVD)是全球主要死因之一。与心脏病发展相关的最重要风险因素包括遗传和环境因素,如高血压、高胆固醇血症、糖尿病、吸烟和肥胖。冠状动脉疾病在CVD死亡中占比最高,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。各种形式心血管疾病的病因、预防和治疗仍是生物医学研究的活跃领域,每周都有数百项科学研究发表。构建心血管疾病动物模型是用于了解发病机制以及设计和测试新疗法的主要方法。在此,我们将聚焦于利用一种原产于东南亚的小型热带淡水鱼——斑马鱼(Danio rerio),在寻找心血管疾病的遗传病因和分子机制以及治疗这些疾病的新药方面的最新进展。斑马鱼已成为一种高通量但低成本的模式生物,它结合了正向和反向遗传学以及表型驱动药物筛选的优势。非侵入性成像可对心血管表型进行体内分析。全基因组关联研究中候选基因的功能验证已证实了多个基因在心血管疾病病理生理学中的作用。此外,斑马鱼心脏在其一生中都保持再生能力,为理解人类心脏再生提供了新的见解。

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