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oai:repisalud.isciii.es:20.500.12105/64912024-09-27T08:24:15Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2018-03 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. 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 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