Zebrafish as a tractable model of human cardiovascular disease.

George Bowley,Jovana Serbanovic-Canic,Freek Van Eeden,Elizabeth Kugler,Paul C Evans,Allan Lawrie,Rob Wilkinson,Emily S Noël,Tim J A Chico

doi:10.1111/bph.15473

Abstract

Mammalian models including non-human primates, pigs and rodents have been used extensively to study the mechanisms of cardiovascular disease. However, there is an increasing desire for alternative model systems that provide excellent scientific value while replacing or reducing the use of mammals. Here, we review the use of zebrafish, Danio rerio, to study cardiovascular development and disease. The anatomy and physiology of zebrafish and mammalian cardiovascular systems are compared, and we describe the use of zebrafish models in studying the mechanisms of cardiac (e.g. congenital heart defects, cardiomyopathy, conduction disorders and regeneration) and vascular (endothelial dysfunction and atherosclerosis, lipid metabolism, vascular ageing, neurovascular physiology and stroke) pathologies. We also review the use of zebrafish for studying pharmacological responses to cardiovascular drugs and describe several features of zebrafish that make them a compelling model for in vivo screening of compounds for the treatment cardiovascular disease. LINKED ARTICLES: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc.

Highlights

The purpose of this review is to provide an overview on the use of zebrafish models of cardiovascular physiology and disease
We summarize zebrafish models of vascular pathology with focus on endothelial dysfunction and atherosclerosis, lipid metabolism, vascular ageing, neurovascular
Despite the relative structural simplicity of the zebrafish heart compared with that of mammals, ECG analysis of adult zebrafish reveals that action potential dynamics of adult zebrafish cardiomyocytes is highly similar to human (Figure 3) (Lin et al, 2018; Liu et al, 2016; Nemtsas et al, 2010)

Summary

Introduction

The purpose of this review is to provide an overview on the use of zebrafish models of cardiovascular physiology and disease. Zebrafish DCM models have been generated through pharmacological induction by administering the K+ channel blocker terfenadine to embryos (Gu et al, 2017), whereas a zebrafish model of ACM was developed using cardiomyocyte-driven expression of a plakoglobin disease variant, resulting in cardiomegaly and thinning of atrial and ventricular walls in early-adult fish (Asimaki et al, 2014).

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