Modeling Cardiovascular Disease in the Zebrafish

Chico, Timothy J. A.; Ingham, Philip W.; Crossman, David C.

doi:10.1016/j.tcm.2008.04.002

Cited by 118 publications

(76 citation statements)

References 45 publications

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“…The zebrafish has been touted as a powerful model for cardiovascular diseases (Chico et al, 2008) and hematopoiesis (Ellett and Lieschke, 2010). Transgenic lines, such as Tg(Fli-1:eGFP) that expresses green fluorescent protein (GFP) in vascular endothelial cells, are especially important tools in the study of the cardiovascular system (Lawson and Weinstein, 2002).…”

Section: Cardiovascular Drug Screensmentioning

confidence: 99%

The developing zebrafish (Danio rerio): A vertebrate model for high‐throughput screening of chemical libraries

Lessman

2011

Birth Defects Research Pt C

136

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The zebrafish, Danio rerio, a small, tropical freshwater species native to Pakistan and India, has become a National Institutes of Health-sanctioned model organism and, due to its many advantages as an experimental vertebrate, it has garnered intense interest from the world's scientific community. Some have labeled the zebrafish, the "vertebrate Drosophila," due to its genetic tractability, small size, low cost, and rapid development. The transparency of the embryo, external development, and the many hundreds of mutant and transgenic lines available add to the allure. Now it appears, the zebrafish can be used for high-throughput screening (HTS) of drug libraries in the discovery process of promising new therapeutics. In this review, various types of screening methods are briefly outlined, as are a variety of screens for different disease models, to highlight the range of zebrafish HTS possibilities. High-content screening (HCS) has been available for cell-based screens for some time and, very recently, HCS is being adapted for the zebrafish. This will allow analysis, at high resolution, of drug effects on whole vertebrates; thus, whole body effects as well as those on specific organs and tissues may be determined.

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Section: Cardiovascular Drug Screensmentioning

confidence: 99%

The developing zebrafish (Danio rerio): A vertebrate model for high‐throughput screening of chemical libraries

Lessman

2011

Birth Defects Research Pt C

136

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“…Instead, some examples will be given in some key therapeutic areas: cancer, diabetes, infectious disease, and inflammation. Other chapters give additional examples, and for recent reviews relating to screening for cardiovascular diseases, see [23] and [24] for cardiac arrhythmias and other conditions in zebrafish, and [25] for an overview of phenotypic assays for atherosclerosis and heart failure.…”

Section: Disease-specific Assaysmentioning

confidence: 99%

Screening Methods for Drug Discovery from Plants

Harvey

2012

Plant Bioactives and Drug Discovery

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Many early pharmacological studies with plant extracts involved injecting samples into rats or mice. The so-called hippocratic screening [1] was widely used. It typically involves administration of several different doses of test substance to small groups of animals and then observing behavior and looking for obvious symptoms at regular intervals for a period of up to 24 h. A systematic system for scoring observations relating to toxicity and to effects on the CNS has been developed as the Irwin test [2]. Such assays are expensive in terms of time and consumables, and they also require relatively large amounts of plant extract. They are more likely to be useful in assessing potential toxic effects than in revealing novel drug effects.Model organisms can be used instead of rodents. Nematode worms (Caenorhabditis elegans), fruit flies (Drosophila melanogaster), and zebrafish (Danio rerio) have all been used in drug discovery (see [3] for a review). Extracts of some traditionally used medicinal plants have been tested on nematodes for antioxidant activities and effects on aging [4][5][6]. Zebrafish embryos are attracting attention because they are vertebrates and many stages of their development can be readily visualized (e.g., [7][8][9]). They are suitable for screening plant extracts in 96-well microtiter plates [10]. Embryos can be exposed to test substances and observed for the development of unusual phenotypes, or disease models can be created in the embryos and samples tested for their ability to modify the expression of the disease (see [3] for examples of disease models in such organisms).

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“…Unlike the double circulation in mammals, the fish heart is two-chambered, consisting of an atrium and a ventricle separated by an atrioventricular valve. The chambers are composed of myocardium and endocardium that initially migrated to form a single heart tube derived from cardiac precursor cells (Chico et al, 2008). Blood development from hematopoietic progenitors starts around 12hpf (hours post fertilization) (Amatruda and Zon, 1999), simultaneous with early cardiac and (Lawson and Weinstein, 2002b The 3dpf (days post fertilization) vasculature of the zebrafish is shown in Figure 1 (Isogai et al, 2001).…”

Section: Zebrafish Cardiovascular Anatomy and Developmentmentioning

confidence: 99%