The heart is still immature, but the major components, such as the bulbous arteriosus, pro-epicardium, and cardiac valves, are formed. From 48 hpf, the ventricle and the atrium become morphologically distinguishable as two separate chambers. At this stage, the irregular cardiomyocyte contractions became coordinated, with an increase of sequential contractions from the atrium and the ventricle, in relation to cardiac development. After the formation, the tube folds toward the right side, becoming the future ventricle, positioned on the opposite side with respect to the atrium, on the left side. The disc elongation generates a heart tube, that is completely formed at 28 hpf, while the cardiogenic differentiation continues. Zebrafish Cardiovascular System: Morphogenesis and Physiology A detailed scheme of the zebrafish life cycle is reported in Figure 1. At ~3 months, zebrafish are sexually mature and are considered adults. At ~6 weeks, zebrafish change their pigment patterns and their fins gain the characteristic of a juvenile appearance. After 5 days, zebrafish begin to be considered experimental animals. During this phase, the morphogenesis is completed and the larvae lose transparency and develop pigmentations. The hatching time can occur between 48 and 72 hpf. After the formation of the head, fins, circulatory, and other primary systems, at 24 hpf, the heart initiates cardiac contraction. During the stage between 10 and 24 hpf, the body of the embryo increases quickly and the sensory tissue start to form. Embryos develop synchronously and extremely rapidly. A single breeding couple produces hundreds of eggs, where the external fertilization and the transparency of embryos allow us to explore the morphology and function of developing organs by light microscopy. The zebrafish life cycle is distinguished by four main stages: the embryo, until 50 h post-fertilization (hpf) larva, until metamorphosis at ~28 dpf the juvenile, from ~3 months until the end of puberty and the adult stage. Many genes in zebrafish are orthologous to humans, but are present in two copies, creating another molecular pathway with different effects than the main one. The extremely rapid development could be a disadvantage, where the screening in zebrafish appears as a running-away train, requiring a perfect experiment setting to have the right exposure time. The lack of maternal-embryo interaction during gestation and the presence, up to 48–72 hpf, of the chorion, may create problems for drug permeability. Like all animal models, zebrafish also present some disadvantages. This, together with the ease of making transgenic models, provides the generation of gene expression and cell-specific reporter lines to follow real-time in vivo experiments, useful for the study of physiological and pathological conditions. Generally, hundreds of embryos can be easily housed in a standard aquarium, allowing not only a reduction of housing space and testing in reasonable sample sizes but also a very high number of replicates at one time. More specifically, embryonic cardiac development and physiological responses to exposure to numerous toxin substances are similar to those observed in mammals, making zebrafish an ideal model to study cardiac development, toxicity, and cardiovascular disease. The high conservation of gene function, low cost, small size, rapid growth, and easiness of genetic manipulation are just some of the features of this experimental model. Over the last few decades, zebrafish has become a powerful non-mammalian model to study alterations associated with human disease. Mammalian models, sharing structural and functional similarities with humans, have been widely used to study cardiovascular disease mechanisms and test new therapies, but many of them are rather expensive and difficult to manipulate. The gradual decline of the kidney leads to the accumulation of uremic solutes with a negative effect on every organ, especially on the cardiovascular system. Cardiovascular events are the main mortality cause in CKD, with a cardiovascular risk 10 times higher in these patients than the rate observed in healthy subjects. About 10% of the general population is affected by CKD, representing the sixth cause of death in the world. Chronic kidney disease (CKD) is an increasing health care problem.
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