Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO

Andrea Fuente-Alonso, Marta Toral, Alvaro Alfayate, María Jesús Ruiz-Rodríguez, Elena Bonzón-Kulichenko, Gisela Teixido-Tura, Sara Martínez-Martínez, María José Méndez-Olivares, Dolores López-Maderuelo, Ileana González-Valdés, Eusebio Garcia-Izquierdo, Susana Mingo, Carlos E. Martín, Laura Muiño-Mosquera, Julie Backer, J. Francisco Nistal, Alberto Forteza, Arturo Evangelista, Jesús Vázquez, Miguel R. Campanero () and Juan Miguel Redondo ()
Additional contact information
Andrea Fuente-Alonso: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Marta Toral: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Alvaro Alfayate: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
María Jesús Ruiz-Rodríguez: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Elena Bonzón-Kulichenko: Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
Gisela Teixido-Tura: Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
Sara Martínez-Martínez: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
María José Méndez-Olivares: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Dolores López-Maderuelo: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Ileana González-Valdés: Cardiovascular Proteomics Laboratoy, CNIC
Eusebio Garcia-Izquierdo: Hospital Universitario Puerta de Hierro
Susana Mingo: Hospital Universitario Puerta de Hierro
Carlos E. Martín: Hospital Universitario Puerta de Hierro
Laura Muiño-Mosquera: Ghent University Hospital
Julie Backer: Ghent University Hospital
J. Francisco Nistal: Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
Alberto Forteza: Hospital Universitario Puerta de Hierro
Arturo Evangelista: Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
Jesús Vázquez: Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
Miguel R. Campanero: Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
Juan Miguel Redondo: Centro Nacional de Investigaciones Cardiovasculares (CNIC)

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract Thoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention as the only available treatment. Here, we show that nitric oxide (NO) signaling dysregulates actin cytoskeleton dynamics in Marfan Syndrome smooth muscle cells and that NO-donors induce Marfan-like aortopathy in wild-type mice, indicating that a marked increase in NO suffices to induce aortopathy. Levels of nitrated proteins are higher in plasma from Marfan patients and mice and in aortic tissue from Marfan mice than in control samples, indicating elevated circulating and tissue NO. Soluble guanylate cyclase and cGMP-dependent protein kinase are both activated in Marfan patients and mice and in wild-type mice treated with NO-donors, as shown by increased plasma cGMP and pVASP-S239 staining in aortic tissue. Marfan aortopathy in mice is reverted by pharmacological inhibition of soluble guanylate cyclase and cGMP-dependent protein kinase and lentiviral-mediated Prkg1 silencing. These findings identify potential biomarkers for monitoring Marfan Syndrome in patients and urge evaluation of cGMP-dependent protein kinase and soluble guanylate cyclase as therapeutic targets.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-22933-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22933-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-22933-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().