Zebrafish as a Model to Study Vascular Elastic Fibers and Associated Pathologies

Abstract

Many extensible tissues such as skin, lungs, and blood vessels require elasticity to function properly. The recoil of elastic energy stored during a stretching phase is provided by elastic fibers, which are mostly composed of elastin and fibrillin-rich microfibrils. In arteries, the lack of elastic fibers leads to a weakening of the vessel wall with an increased risk to develop cardiovascular defects such as stenosis, aneurysms, and dissections. The development of new therapeutic molecules involves preliminary tests in animal models that recapitulate the disease and whose response to drugs should be as close as possible to that of humans. Due to its superior in vivo imaging possibilities and the broad tool kit for forward and reverse genetics, the zebrafish has become an important model organism to study human pathologies. Moreover, it is particularly adapted to large scale studies, making it an attractive model in particular for the first steps of investigations. In this review, we discuss the relevance of the zebrafish model for the study of elastic fiber-related vascular pathologies. We evidence zebrafish as a compelling alternative to conventional mouse models.

A synthetic elastic protein as molecular prosthetic candidate to strengthen vascular wall elasticity

“…The in vitro experiments suggest that SEP behaves as an analogue of hTE. To go further and initiate in vivo studies, we chose to use the zebrafish model that we recently reported as a relevant tool in the analyses of cardiovascular issues [39]. Specifically, we used the transgenic zebrafish reporter line Tg( fli1a :eGFP)/Casper, whose endothelial cells are fluorescent and enable vessel development observation in real time.…”

Syndecan-4 is required for early-stage repair responses during zebrafish heart regeneration

“…Comparing regenerative and non-regenerative hearts can inform treatment strategies for human heart diseases. In healthy adult humans, ventricular blood pressure is maintained at 120 mmHg, while in adult zebrafish, it is estimated to be only 2.5 mmHg [ 29 ]. Mammals deposit thick collagen layers to strengthen the ventricular wall against high blood pressure [ 30 ], whereas zebrafish generate a thin, loose collagen-rich scar during early heart regeneration [ 31 ], making the scarring easier to resolve.…”

Animal Disease Models and Patient-iPS-Cell-Derived In Vitro Disease Models for Cardiovascular Biology—How Close to Disease?

“…Additionally, they have a simpler circulatory system than mammals. Although the structure of the heart of zebrafish appears different, some of their electrocardiogram parameters are more comparable to those of humans than those of mice; heart rates are 120–180 beats per minute (bpm) in zebrafish, 300–600 bpm in mice, and 60–100 bpm in humans [ 3 , 4 , 5 ]. Both humans and zebrafish generate a repolarizing current during action potential (AP), using a similar rapidly activating delayed rectifier potassium current.…”

“…In the field of cardiovascular research, different environments may result in different heart structures; for example, zebrafish have one atrium and one ventricle, whereas mice and humans have two atria and two ventricles. The characteristics of heart function also vary [ 3 , 4 , 5 ]. Nevertheless, mice and rodents are most often used as models of cardiovascular disease because they are easy to handle, have lower upkeep costs, and maintain stricter strains, resulting in fewer genetic differences.…”