2026-07-23T18:45:34Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/67392024-11-29T21:54:08Zcom_20.500.12105_19604com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_19605col_20.500.12105_19597
Repisalud
author
Villahoz, Silvia
author
Yunes-Leites, Paula Sofia
author
Mendez-Barbero, Nerea
author
Urso, Katia
author
Bonzon-Kulichenko, Elena
author
Ortega Jimenez, Sagrario
author
Nistal, J Francisco
author
Vazquez, Jesus
author
Offermanns, Stefan
author
Redondo, Juan Miguel
author
Campanero, Miguel R
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
Fundación La Marató TV3
funder
Marfan Foundation
funder
Ministerio de Sanidad y Consumo (España)
funder
Fundación ProCNIC
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
2018-11-29T10:07:57Z
2018-11-29T10:07:57Z
2018-11-15
Nat Commun. 2018; 9(1): 4795.
10.1038/s41467-018-07071-7
2041-1723
2041-1723
Nature communications
30442942
http://hdl.handle.net/20.500.12105/6739
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.
eng
SYNDROME CRITICAL REGION
CALCINEURIN INHIBITOR DSCR1
VASCULAR SMOOTH-MUSCLE
PEPTIDE IDENTIFICATION
STRIATED-MUSCLES
OXIDATIVE STRESS
CELL-MIGRATION
TUMOR-GROWTH
1 GENE
MICE
Conditional deletion of Rcan1 predisposes to hypertension-mediated intramural hematoma and subsequent aneurysm and aortic rupture
journal article
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ConditionaldeletionofRcan1_2018_MOESM1_ESM.pdf
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Conditionaldeletionof Rcan1_2018.pdf
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ConditionaldeletionofRcan1_2018_MOESM1_ESM.pdf.txt
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Conditionaldeletionof Rcan1_2018.pdf.txt