2026-05-22T16:47:04Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/64912024-09-27T08:24:15Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Molina-Sanchez, Pedro
author
del Campo, Lara
author
Esteban, Vanesa
author
Rius, Cristina
author
Chevre, Raphael
author
Fuster, Jose J.
author
Ferrer, Mercedes
author
Redondo, Juan Miguel
author
Andres, Vicente
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ministerio de Educación (España)
funder
Centro de Investigación Biomédica en Red - CIBERCV (Enfermedades Cardiovasculares)
funder
Fundación ProCNIC
2018-10-17T10:56:07Z
2018-10-17T10:56:07Z
2018-03
J Mol Cell Cardiol. 2018; 116:5-15
10.1016/j.yjmcc.2018.01.010
1095-8584
0022-2828
Journal of molecular and cellular cardiology
29408196
http://hdl.handle.net/20.500.12105/6491
Phosphorylation at serine 10 (S10) is the major posttranslational modification of the tumor suppressor p27, and is reduced in both human and mouse atherosclerosis. Moreover, a lack of p27-phospho-S10 in apolipoprotein E-null mice (apoE-/-) leads to increased high-fat diet-induced atherosclerosis associated with endothelial dysfunction and augmented leukocyte recruitment. In this study, we analyzed whether p27-phospho-S10 modulates additional endothelial functions and associated pathologies. Defective p27-phospho-S10 increases COX-2 activity in mouse aortic endothelial cells without affecting other key regulators of vascular reactivity, reduces endothelium-dependent dilation, and increases arterial contractility. Lack of p27-phospho-S10 also elevates aortic COX-2 expression and thromboxane A2 production, increases aortic lumen diameter, and aggravates angiotensin II-induced abdominal aortic aneurysm development in apoE-/- mice. All these abnormal responses linked to defective p27-phospho-S10 are blunted by pharmacological inhibition of COX-2. These results demonstrate that defective p27-phospho-S10 modifies endothelial behavior and promotes aneurysm formation via COX-2 activation.
eng
Aneurysm
Cox-2
Endothelial cell
Vascular contractility
p27
p27 phosphorylation at serine 10
Defective p27 phosphorylation at serine 10 affects vascular reactivity and increases abdominal aortic aneurysm development via Cox-2 activation
journal article
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Defectivep27PhosphorylationSerine_2018_FIG.pdf.txt
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