visitant ::
identificació
|
|||||||||||||||
Cerca | Lliura | Ajuda | Servei de Biblioteques | Sobre el DDD | Català English Español |
Pàgina inicial > Articles > Articles publicats > Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO |
Data: | 2021 |
Resum: | 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. Aortic aneurysm and dissection, the major problem linked to Marfan syndrome (MFS), lacks effective pharmacological treatment. Here, the authors show that the NO pathway is overactivated in MFS and that inhibition of guanylate cyclase and cGMP-dependent protein kinase reverts MFS aortopathy in mice. |
Ajuts: | Agencia Estatal de Investigación SAF2017-88881R Ministerio de Economía y Competitividad SAF2015-636333R Agencia Estatal de Investigación RTI2018-099246-B-I00 Ministerio de Economía y Competitividad SEV-2015-0505 |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Aneurysm ; Aortic diseases |
Publicat a: | Nature communications, Vol. 12 (may 2021) , ISSN 2041-1723 |
18 p, 6.2 MB |