Molina-Sanchez, Pedrodel Campo, LaraEsteban, VanesaRius, CristinaChevre, RaphaelFuster, Jose J.Ferrer, MercedesRedondo, Juan MiguelAndres, Vicente2018-10-172018-10-172018-03J Mol Cell Cardiol. 2018; 116:5-150022-2828http://hdl.handle.net/20.500.12105/6491Phosphorylation 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.engAMhttp://creativecommons.org/licenses/by-nc-sa/4.0/AneurysmCox-2Endothelial cellVascular contractilityp27p27 phosphorylation at serine 10Atribución-NoComercial-CompartirIgual 4.0 Internacional294081961165-1510.1016/j.yjmcc.2018.01.0101095-8584Journal of molecular and cellular cardiologyopen access