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Updated: Oct 21, 2025
Measurement of Endothelium-Dependent Vasorelaxation in the Mouse Thoracic Aorta Using Tensometric Small Volume Chamber Myography
Published on: August 12, 2022
Nitric oxide in the Marfan vasculature: Friend or foe?
Arash Y Tehrani1, Marco A Ciufolini2, Pascal Bernatchez1
1Centre for Heart + Lung Innovation, St. Paul's Hospital, Department of Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia (UBC), Vancouver, Canada.
Abstract:
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.
Insights
Marfan syndrome (MFS) involves aortic root widening due to FBN1 gene mutations affecting elastic fibers. Nitric oxide (NO) pathway dysfunction contributes to this, and therapies targeting NO homeostasis may improve outcomes.
Area of Science:
- Cardiovascular Biology
- Genetics
- Vascular Medicine
Background:
- Marfan syndrome (MFS) is a genetic connective tissue disorder caused by FBN1 gene mutations.
- It leads to progressive aortic root widening, increasing risks of dissection and rupture.
- Current antihypertensive treatments show limited efficacy in slowing aortic dilation.
Purpose of the Study:
- To review the role of nitric oxide synthase (NOS)-related vascular changes in MFS pathogenesis.
- To explore how these changes contribute to aortic root widening.
- To discuss therapeutic strategies targeting NO homeostasis for aortic root stabilization.
Main Methods:
- Review of recent evidence on NOS-related vascular changes in MFS.
- Analysis of the impact of NO dysfunction on aortic remodeling.
- Evaluation of existing and experimental therapies, including lifestyle interventions.
Main Results:
- MFS involves unique vascular dysfunction linked to NOS-related changes.
- This dysfunction is a likely causal factor in aortic root widening.
- Optimizing NO homeostasis presents a potential therapeutic avenue.
Conclusions:
- Nitric oxide (NO) pathway alterations are critical in Marfan syndrome-associated aortopathy.
- Targeting NO homeostasis offers a promising strategy to improve aortic root stability.
- Further research into NO-related therapies could enhance outcomes for MFS patients.
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