Insights into elastin fiber fragmentation: Mechanisms and treatment of aortic aneurysm in Marfan syndrome.
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by fibrillin 1 (FBN1) gene mutations that results in defects in the skeletal, ocular, and cardiovascular systems. Aortic aneurysm is the leading cause of premature mortality in untreated MFS patients. Elastin fiber fragmentation in the aortic vessel wall is a hallmark of MFS-associated aortic aneurysms. FBN1 mutations result in FBN1 fragments that also contribute to elastin fiber fragmentation. Although recent research has advanced our understanding of MFS, the contribution of elastin fiber fragmentation to the pathogenesis of aneurysm formation remains poorly understood. This review provides a comprehensive overview of the molecular mechanisms of elastin fiber fragmentation and its role in the pathogenesis of aortic aneurysm progression. Increased comprehension of elastin fragmentation has significant clinical implications for developing targeted interventions to block aneurysm progression, which would benefit not only individuals with Marfan syndrome but also other patients with aneurysms. Moreover, this review highlights an overlooked connection between inhibiting aneurysm and the restoration of elastin fibers in the vessel wall with various aneurysm inhibitors, including drugs and chemicals. Investigating the underlying molecular mechanisms could uncover innovative therapeutic strategies to inhibit elastin fragmentation and prevent the progression of aneurysms.