Using Zebrafish for High-Throughput Screening of Novel Cardiovascular Drugs

JACC. Basic to Translational Science
Aaron Kithcart, Calum A Macrae

Abstract

Cardiovascular diseases remain a major challenge for modern drug discovery. The diseases are chronic, complex, and the result of sophisticated interactions between genetics and environment involving multiple cell types and a host of systemic factors. The clinical events are often abrupt, and the diseases may be asymptomatic until a highly morbid event. Target selection is often based on limited information, and though highly specific agents are often identified in screening, their final efficacy is often compromised by unanticipated systemic responses, a narrow therapeutic index, or substantial toxicities. Our understanding of complexity of cardiovascular disease has grown dramatically over the past 2 decades, and the range of potential disease mechanisms now includes pathways previously thought only tangentially involved in cardiac or vascular disease. Despite these insights, the majority of active cardiovascular agents derive from a remarkably small number of classes of agents and target a very limited number of pathways. These agents have often been used initially for particular indications and then discovered serendipitously to have efficacy in other cardiac disorders or in a manner unrelated to their original mechanism of ...Continue Reading

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Mar 6, 2019·PloS One·Omar T HammoudaThomas Thumberger
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Apr 1, 2021·British Journal of Pharmacology·George BowleyJovana Serbanovic-Canic
Jun 25, 2021·Cardiovascular Research·Katherine M Ross StewartMairi Brittan

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Methods Mentioned

BETA
targeted knock-in
transgenic

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