APA
Esteban, Vanesa & Méndez Barbero, Nerea & Jiménez Borreguero, Luis Jesús & Roqué, Mercè & Novensá, Laura & García Redondo, Ana Belén & Salaices, Mercedes & Vila, Luis & Arbonés, María L. & Campanero, Miguel R. & Redondo, Juan Miguel (2011-09 ) .Regulator of calcineurin 1 mediates pathological vascular wall remodeling.
ISO 690
Esteban, Vanesa & Méndez Barbero, Nerea & Jiménez Borreguero, Luis Jesús & Roqué, Mercè & Novensá, Laura & García Redondo, Ana Belén & Salaices, Mercedes & Vila, Luis & Arbonés, María L. & Campanero, Miguel R. & Redondo, Juan Miguel. 2011-09 .Regulator of calcineurin 1 mediates pathological vascular wall remodeling.
https://hdl.handle.net/20.500.12080/45601
Resumen:
Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase
the vessel lumen. The identification of molecules involved in vessel remodeling could aid the
development of improved treatments for these pathologies. Angiotensin II (AngII) is a key
effector of aortic wall remodeling that contributes to aneurysm formation and restenosis
through incompletely defined signaling pathways. We show that AngII induces vascular
smooth muscle cell (VSMC) migration and vessel remodeling in mouse models of restenosis
and aneurysm. These effects were prevented by pharmacological inhibition of calcineurin
(CN) or lentiviral delivery of CN-inhibitory peptides. Whole-genome analysis revealed >1,500
AngII-regulated genes in VSMCs, with just 11 of them requiring CN activation. Of these, the
most sensitive to CN activation was regulator of CN 1 (Rcan1). Rcan1 was strongly
activated by AngII in vitro and in vivo and was required for AngII-induced VSMC migration.
Remarkably, Rcan1¿/¿ mice were resistant to AngII-induced aneurysm and restenosis.
Our results indicate that aneurysm formation and restenosis share mechanistic elements
and identify Rcan1 as a potential therapeutic target for prevention of aneurysm and
restenosis progression.