Alterations in the FBN1 gene are responsible for causing Marfan Syndrome (MFS), a connective tissue disease characterized for malformation of the microfibrils, which are molecules with an important structural role that act in several functions, including elastin deposition and TGF-² storage. One of MFS's greatest complications is aneurism formation, mainly in the aorta, which can eventually lead to dissection and rupture of the blood vessels. Alterations in the microfibril network affect the physiology of both the extracellular matrix and the distinct cell types. Of these cell types, one greatly affected by MFS is the endothelium, responsible in the communication between the blood flow and the inside of the vessels, as well as promoting the vascular muscle smooth cells relaxation. It is believed that some of the physiological changes caused by MFS are related to cell maturation and proliferation, which can contribute in aneurism formation. Some models have been proposed to help understand the phenotypical variability of the disease: one is the negative dominant model, in which the mutated protein is expressed leading to a negative dominance effect because of the interference in the microfibrils' regular structure; and the haploinsufficient model, in which the observed phenotypes are caused by mutations leading to one of the FBN1 alleles's mRNA degradation. In order to understand the cellular and molecular mechanisms involved in this disease, our group has generated hiPSC lineages with mutations in the FBN1 gene which mimetize the negative dominant and haploinsufficient models. In this study we hope to obtain and characterize endothelial cells from this lineages and study the effect of these mutations in cell proliferation. We believe that this study can help in the understanding of the cardiovascular changes in MFS.
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