Molina-Sánchez, PedroCampo, Lara delEsteban, VanesaRius Leiva, CristinaChèvre, RaphaëlFuster, José JavierFerrer, MercedesRedondo, Juan MiguelAndrés, Vicente2018-10-202018-10-202018Molina-Sánchez, P., Del Campo, L., Esteban, V., Rius, C., Chèvre, R., Fuster, J. J., ... & Andrés, V. (2018). Defective p27 phosphorylation at serine 10 affects vascular reactivity and increases abdominal aortic aneurysm development via Cox-2 activation. Journal of Molecular and Cellular Cardiology, 116, 5-15. DOI:10.1016/j.yjmcc.2018.01.0100022-28281095-8584http://hdl.handle.net/11268/7477Phosphorylation 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.engjournal article10.1016/j.yjmcc.2018.01.010restricted accessAneurisma abdominalEnfermedad cardiovascular