Zebrafish models of cardiovascular disease

Despina Bournele, Dimitris Beis

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.