Vol. 34, Nš 1

Critical analysis of aortic dysmorphism in Marfan Syndrome

SOUZA, R. B.; CASSIANO, L. L.; LIBERATORE, A. M. A.; TEDESCO, R. C.; KOH, I. H. J. ; MARTINS, A. M. C. R. P. F.; VRETOS, C.; ALONSO, L. G

KEYWORDS: Marfan syndrome, arterial wall, morphology, extracellular matrix, aneurysm, dissecting aneurysm.

ABSTRACT: Introduction: Marfan syndrome (OMIM #154700) was described for the first time in 1896 by Antoine Bernard?Jean Marfan. It is characterized by its autosomal dominant inheritance pattern, affects 1:5000 of those born alive, and involves the gene that codifies the structural protein fribrillin-1. Fibrillin-1 is critical for the formation of the elastic system backbone and for the negative regulation of the cytokine transforming growth factor beta 1 (TGF-?1). In the syndrome this fibrillar component causes the degeneration of the fibers of the elastic system, which no longer sequesters matrix TGF-?, causing disorganization of the collagen fibers and vascular smooth muscles. The disease affects mainly the cardiovascular system, cardiovascular problems being the main cause of death. This is because arteries have large amounts of elastic fibers that rupture in an adverse process, causing mainly dissections and aneurisms, which have been better clarified in experimental studies with mice. Objective: The objective of this study was to conduct an etiopathogenic and molecular review to describe the advances in the understanding of blood vessel dysmorphism in the syndrome, especially of the aorta. Materials and Methods: For this purpose the literature of the last 35 years was extensively reviewed. Conclusion: The origin of the aortic dysmorphism in the syndrome stems from a number of events that begin with the mutation of the gene fibrillin-1, causing fragmentation of the aortic elastic fibers. Excess cytokine TGF-? increases the amount of metalloproteinases and of vascular smooth muscle cell apoptosis, leading to matrix remodeling and increasing the susceptibility of the vessel to an aneurysm or dissecting process.