The NO signalling pathway in aortic aneurysm and dissection.

Abstract

Recent studies have shown that NO is a central mediator in diseases associated with thoracic aortic aneurysm, such as Marfan syndrome. The progressive dilation of the aorta in thoracic aortic aneurysm ultimately leads to aortic dissection. Unfortunately, current medical treatments have neither halt aortic enlargement nor prevented rupture, leaving surgical repair as the only effective treatment. There is therefore a pressing need for effective therapies to delay or even avoid the need for surgical repair in thoracic aortic aneurysm patients. Here, we summarize the mechanisms through which NO signalling dysregulation causes thoracic aortic aneurysm, particularly in Marfan syndrome. We discuss recent advances based on the identification of new Marfan syndrome mediators related to pathway overactivation that represent potential disease biomarkers. Likewise, we propose iNOS, sGC and PRKG1, whose pharmacological inhibition reverses aortopathy in Marfan syndrome mice, as targets for therapeutic intervention in thoracic aortic aneurysm and are candidates for clinical trials.

• Authors: Marta Toral, Andrea de la Fuente-Alonso, Miguel R Campanero, Juan Miguel Redondo
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 179 Issue 7 Pg. 1287-1303 (04 2022) ISSN: 1476-5381 [Electronic] England
• PMID: 34599830 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2021 The British Pharmacological Society.

Chemical References

• Cyclic GMP-Dependent Protein Kinase Type I
• Prkg1 protein, mouse

Topics

• Aortic Dissection (complications, surgery)
• Animals
• Aorta
• Aortic Aneurysm (complications)
• Aortic Aneurysm, Thoracic (etiology, prevention & control, surgery)
• Cyclic GMP-Dependent Protein Kinase Type I
• Humans
• Marfan Syndrome (complications, drug therapy, surgery)
• Mice