The pathogenesis of aortopathy in Marfan syndrome and related diseases.

Abstract

Marfan syndrome is a systemic connective tissue disorder that is inherited in an autosomal-dominant pattern with variable penetrance. Although there are many clinical manifestations of this disease, the most life threatening are cardiovascular complications, including mitral valve prolapse and aortic root aneurysm. When the primary defect was discovered in the fibrillin-1 gene, it was hypothesized that mutations in fibrillin-1 resulted in a weakened and disordered elastic architecture. However, recent evidence has suggested that the Marfan syndrome is caused by more than just a disordered microfibril matrix. Interest was stimulated when it was discovered that fibrillin-1 mutations enhanced the release of sequestered latent transforming growth factor-beta, a well-described mediator of vascular remodeling. This article focuses on the pathophysiology of aortopathy in the Marfan syndrome and related diseases, with special emphasis on the role of transforming growth factor-beta in mediating the pathogenesis of this disease.

• Authors: Jeffrey A Jones, John S Ikonomidis
• Journal: Current cardiology reports (Curr Cardiol Rep) Vol. 12 Issue 2 Pg. 99-107 (Mar 2010) ISSN: 1534-3170 [Electronic] United States
• PMID: 20425163 (Publication Type: Journal Article, Review)

Chemical References

• FBN1 protein, human
• Fibrillin-1
• Fibrillins
• Microfilament Proteins
• Transforming Growth Factor beta

Topics

• Aortic Dissection (etiology, pathology)
• Aortic Aneurysm, Thoracic (etiology, pathology)
• Fibrillin-1
• Fibrillins
• Humans
• Marfan Syndrome (complications, genetics, pathology)
• Microfilament Proteins (genetics)
• Mitral Valve Prolapse (etiology, pathology)
• Mutation
• Risk Factors
• Signal Transduction
• Transforming Growth Factor beta (genetics)