On Zebrafish Disease Models and Matters of the Heart

Abstract

Coronary artery disease (CAD) is the leading form of cardiovascular disease (CVD), which is the primary cause of mortality worldwide. It is a complex disease with genetic and environmental risk factor contributions. Reports in human and mammalian models elucidate age-associated changes in cardiac function. The diverse mechanisms involved in cardiac diseases remain at the center of the research interest to identify novel strategies for prevention and therapy. Zebrafish (Danio rerio) have emerged as a valuable vertebrate model to study cardiovascular development over the last few decades. The facile genetic manipulation via forward and reverse genetic approaches combined with noninvasive, high-resolution imaging and phenotype-based screening has provided new insights to molecular pathways that orchestrate cardiac development. Zebrafish can recapitulate human cardiac pathophysiology due to gene and regulatory pathways conservation, similar heart rate and cardiac morphology and function. Thus, generations of zebrafish models utilize the functional analysis of genes involved in CAD, which are derived from large-scale human population analysis. Here, we highlight recent studies conducted on cardiovascular research focusing on the benefits of the combination of genome-wide association studies (GWAS) with functional genomic analysis in zebrafish. We further summarize the knowledge obtained from zebrafish studies that have demonstrated the architecture of the fundamental mechanisms underlying heart development, homeostasis and regeneration at the cellular and molecular levels.

An Overview of Methods for Cardiac Rhythm Detection in Zebrafish

“…Additionally, biological characteristics, ease of genetic manipulation, facilitation of chemical screening, and genetic similarity to humans are features that contributed to zebrafish as a versatile animal model for cardiovascular research. Previously, zebrafish have been generated to study lipid metabolism and hypercholesteremia, major risk factors for cardiovascular disease [3]. Furthermore, Chen et al reported mutations in zebrafish, useful for in-depth cardiac development research [7].…”

Streamlining drug discovery assays for cardiovascular disease using zebrafish

“…Nevertheless, despite its simplicity, genes, molecular signaling cascades and cellular processes that orchestrate the development of the heart are grossly conserved between zebrafish and mammals including humans. Additionally, cardiac physiology including heart rate, cardiac contractility, mechano-transduction as well as electrophysiological properties is highly similar between zebrafish and humans [18,[22][23][24]. For example, 3 days post-fertilization, the zebrafish heartbeats 150 times per minute which is much closer to the human situation than the mouse heart that beats appr.…”

Zebrafish cardiac regeneration—looking beyond cardiomyocytes to a complex microenvironment

“…It is important to note that following cardiac damage, such as MI (humans) or cryoinjury (zebrafish), the initial phases from injury to repair and scarring are conserved, further strengthening the value of the zebrafish as a powerful tool to understand the limiting factors preventing mammalian regeneration ( Fig. 1 and reviewed by Giardoglou and Beis 2019). Both human and zebrafish repair involves an initial inflammatory phase (defined by the recruitment of immune cells and the clearance of cellular debris by phagocytosis) followed by a reparative phase characterised by deposition of collagen and other extracellular matrix (ECM) components and scar formation (Dobaczewski et al 2011;Chablais and Jazwinska 2012).…”