title: Epigenetic regulation of TGF-β1 signalling in dilative aortopathy of the thoracic ascending aorta.
abstract: The term 'epigenetics' refers to heritable, reversible DNA or histone modifications that affect gene expression without modifying the DNA sequence. Epigenetic modulation of gene expression also includes the RNA interference mechanism. Epigenetic regulation of gene expression is fundamental during development and throughout life, also playing a central role in disease progression. The transforming growth factor β1 (TGF-β1) and its downstream effectors are key players in tissue repair and fibrosis, extracellular matrix remodelling, inflammation, cell proliferation and migration. TGF-β1 can also induce cell switch in epithelial-to-mesenchymal transition, leading to myofibroblast transdifferentiation. Cellular pathways triggered by TGF-β1 in thoracic ascending aorta dilatation have relevant roles to play in remodelling of the vascular wall by virtue of their association with monogenic syndromes that implicate an aortic aneurysm, including Loeys-Dietz and Marfan's syndromes. Several studies and reviews have focused on the progression of aneurysms in the abdominal aorta, but research efforts are now increasingly being focused on pathogenic mechanisms of thoracic ascending aorta dilatation. The present review summarizes the most recent findings concerning the epigenetic regulation of effectors of TGF-β1 pathways, triggered by sporadic dilative aortopathy of the thoracic ascending aorta in the presence of a tricuspid or bicuspid aortic valve, a congenital malformation occurring in 0.5-2% of the general population. A more in-depth comprehension of the epigenetic alterations associated with TGF-β1 canonical and non-canonical pathways in dilatation of the ascending aorta could be helpful to clarify its pathogenesis, identify early potential biomarkers of disease, and, possibly, develop preventive and therapeutic strategies.
authors.affiliation: Experimental Medicine, Second University of Naples, Naples, Italy amalia.forte@unina2.it.
authors.forename: Amalia
authors.initials: A
authors.lastname: Forte
authors.affiliation: Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Galderisi
authors.affiliation: Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Cipollaro
authors.affiliation: Cardiothoracic Sciences, Second University of Naples, Naples, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: De Feo
authors.affiliation: Cardiothoracic Sciences, Second University of Naples, Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Della Corte
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D001018:Aortic Diseases / Q000235:genetics* / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006801:Humans; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1
keywords: TGF-β1 pathway; aneurysm; bicuspid aortic valve; epigenetics; thoracic ascending aorta