RESUMO
Marfan syndrome (MFS) is a hereditary condition caused by mutations in the FBN1 gene. Genetic mutations in the FBN1 locus impact the function of the encoded protein, Fibrillin 1, a structural molecule forming microfibrils found in the connective tissue. MFS patients develop severe cardiovascular complications including thoracic aortic aneurysm and aortic dissection, which predispose them to an enhanced risk of premature death. Here, we generated two induced pluripotent stem cell (iPSC) lines harboring mutations in the FBN1 gene (p.C1942C>A and c.1954 T>C), directly derived from MFS patients. We have shown that both iPSC lines displayed expression of pluripotency markers, normal karyotype and ability of trilineage differentiation, representing a valuable tool for the identification of new therapeutic strategies for intervening in this disease.
Assuntos
Fibrilina-1 , Células-Tronco Pluripotentes Induzidas , Síndrome de Marfan , Mutação , Síndrome de Marfan/genética , Síndrome de Marfan/patologia , Fibrilina-1/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Humanos , Diferenciação Celular , Linhagem Celular , Masculino , AdipocinasRESUMO
[Figure: see text].
Assuntos
Aterosclerose/etiologia , Desdiferenciação Celular , MicroRNAs/metabolismo , Músculo Liso Vascular/fisiologia , RNA Longo não Codificante/fisiologia , Animais , Aterosclerose/patologia , Movimento Celular , Proliferação de Células , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Vasos Coronários/citologia , Regulação para Baixo , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Metabolismo dos Lipídeos , Camundongos , Músculo Liso Vascular/citologia , Oligonucleotídeos Antissenso , Fenótipo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , TranscriptomaRESUMO
Noncoding RNAs (long noncoding RNAs and small RNAs) are emerging as critical modulators of phenotypic changes associated with physiological and pathological contexts in a variety of cardiovascular diseases (CVDs). Although it has been well established that hereditable genetic alterations and exposure to risk factors are crucial in the development of CVDs, other critical regulators of cell function impact on disease processes. Here we discuss noncoding RNAs have only recently been identified as key players involved in the progression of disease. In particular, we discuss micro RNA (miR)-143/145 since they represent one of the most characterised microRNA clusters regulating smooth muscle cell (SMC) differentiation and phenotypic switch in response to vascular injury and remodelling. MiR143HG is a well conserved long noncoding RNA (lncRNA), which is the host gene for miR-143/145 and recently implicated in cardiac specification during heart development. Although the lncRNA-miRNA interactions have not been completely characterised, their crosstalk is now beginning to emerge and likely requires further research focus. In this review we give an overview of the biology of the genomic axis that is miR-143/145 and MiR143HG, focusing on their important functional role(s) in the cardiovascular system.
