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.

Mineralized collagen gels have been developed as in vitro models to better understand the mechanisms regulating the calcification process and the behavior of a variety of cell types. The vast majority of data are related to stem cells and to osteoblast-like cells, whereas little information is available for dermal fibroblasts, although these cells have been associated with ectopic calcification and consequently to a number of pathological conditions. Therefore, we developed and characterized an enzymatically mineralized collagen gel in which fibroblasts were encapsulated within the 3D structure. MgCl₂ was also added during gel polymerization, given its role as (i) modulator of ectopic calcification; (ii) component of biomaterials used for bone replacement; and (iii) constituent of pathological mineral deposits. Results demonstrate that, in a short time, an enzymatically mineralized collagen gel can be prepared in which mineral deposits and viable cells are homogeneously distributed. MgCl₂ is present in mineral deposits and significantly affects collagen fibril assembly and organization. Consequently, cell shape and the ability of fibroblasts to retract collagen gels were modified. The development of three-dimensional (3D) mineralized collagen matrices with both different structural features and mineral composition together with the use of fibroblasts, as a prototype of soft connective tissue mesenchymal cells, may pave new ways for the study of ectopic calcification.

Most chronic wounds are characterized by varying degrees of hypoxia and low partial pressures of O₂ that may favor the development of the wound and/or delay healing. However, most studies regarding extracellular matrix remodeling in wound healing are conducted under normoxic conditions. Here, we investigated the consequences of hypoxia on elastic network formation, both in a mouse model of pressure-induced hypoxic ulcer and in human primary fibroblasts cultured under hypoxic conditions. In vitro, hypoxia inhibited elastic fiber synthesis with a reduction in fibrillin-2 expression at the mRNA and protein levels. Lysyl oxidase maturation was reduced, concomitant with lower enzymatic activity. Fibrillin-2 and lysyl oxidase could interact directly, whereas the downregulation of fibrillin-2 was associated with deficient lysyl oxidase maturation. Elastic fibers were not synthesized in the hypoxic inflammatory tissues resulting from in vivo pressure-induced ulcer. Tropoelastin and fibrillin-2 were expressed sparsely in hypoxic tissues stained with carbonic anhydrase IX. Different hypoxic conditions in culture resulted in the arrest of elastic fiber synthesis. The present study demonstrated the involvement of FBN2 in regulating elastin deposition in adult skin models and described the specific impact of hypoxia on the elastin network without consequences on collagen and fibronectin networks.