Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/6739
Título
Conditional deletion of Rcan1 predisposes to hypertension-mediated intramural hematoma and subsequent aneurysm and aortic rupture
Autor(es)
Villahoz, Silvia CNIC | Yunes-Leites, Paula Sofia CNIC | Mendez-Barbero, Nerea CNIC | Urso, Katia CNIC | Bonzon-Kulichenko, Elena CNIC | Ortega Jimenez, Sagrario CNIO | Nistal, J Francisco | Vazquez, Jesus CNIC | Offermanns, Stefan | Redondo, Juan Miguel CNIC | Campanero, Miguel R
Fecha de publicación
2018-11-15
Cita
Nat Commun. 2018; 9(1): 4795.
Idioma
Inglés
Tipo de documento
journal article
Resumen
Aortic intramural hematoma (IMH) can evolve toward reabsorption, dissection or aneurysm. Hypertension is the most common predisposing factor in IMH and aneurysm patients, and the hypertensive mediator angiotensin-II induces both in mice. We have previously shown that constitutive deletion of Rcan1 isoforms prevents Angiotensin II-induced aneurysm in mice. Here we generate mice conditionally lacking each isoform or all isoforms in vascular smooth muscle cells, endothelial cells, or ubiquitously, to determine the contribution to aneurysm development of Rcan1 isoforms in vascular cells. Surprisingly, conditional Rcan1 deletion in either vascular cell-type induces a hypercontractile phenotype and aortic medial layer disorganization, predisposing to hypertension-mediated aortic rupture, IMH, and aneurysm. These processes are blocked by ROCK inhibition. We find that Rcan1 associates with GSK-3β, whose inhibition decreases myosin activation. Our results identify potential therapeutic targets for intervention in IMH and aneurysm and call for caution when interpreting phenotypes of constitutively and inducibly deficient mice.
Palabras clave
SYNDROME CRITICAL REGION | CALCINEURIN INHIBITOR DSCR1 | VASCULAR SMOOTH-MUSCLE | PEPTIDE IDENTIFICATION | STRIATED-MUSCLES | OXIDATIVE STRESS | CELL-MIGRATION | TUMOR-GROWTH | 1 GENE | MICE
Versión en línea
DOI
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