Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the FBN1 gene, which encodes fibrillin-1, a protein essential for the formation and stabilization of elastic fibers as well as signaling homeostasis. Progressive aortic root widening is the most serious manifestation of MFS as it can lead to aortic dissection, aneurysm formation and rupture. However, despite their ability to decrease the hemodynamic stress the aorta is subjected to, anti-hypertensive medications often lead to underwhelming reductions in the rate of aortic root dilation, which illustrates how fragmental our understanding of MFS-associated aortic remodeling is. This manuscript summarizes recent evidence that document nitric oxide (NO) synthase (NOS)-related changes to the vasculature during the pathogenesis of MFS and how they result in a unique state of vascular dysfunction that likely plays a causal role in the aortic root widening process. We also review how clinic-approved and experimental therapies as well lifestyle approaches may promote aortic root stability by correcting NO homeostasis, which if properly optimized may improve outcomes in this population afflicted by a notoriously refractory type of aortopathy.
Keywords: Endothelium; Marfan syndrome; Nitric oxide; Nitric oxide synthase; Smooth muscle cells.
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