RT Journal Article
T1 Platelet Content of Nitric Oxide Synthase 3 Phosphorylated At Serine1177 Is Associated with the Functional Response of Platelets to Aspirin
A1 Modrego, Javier
A1 Azcona, Luis
A1 Martín Palacios, Naiara
A1 Zamorano León, José Javier
A1 Segura, Antonio
A1 Rodriguez, Pablo
A1 Guerra, Reddy
A1 Tamargo Menéndez, Juan
A1 Macaya Miguel, Carlos
A1 López Farre, Antonio José
AB Objective: To analyse if platelet responsiveness to aspirin (ASA) may be associated with a different ability of platelets to generate nitric oxide (NO).Patients/methods: Platelets were obtained from 50 patients with stable coronary ischemia and were divided into ASA-sensitive (n = 26) and ASA-resistant (n = 24) using a platelet functionality test (PFA-100).Results: ASA-sensitive platelets tended to release more NO (determined as nitrite + nitrate) than ASA-resistant platelets but it did not reach statistical significance. Protein expression of nitric oxide synthase 3 (NOS3) was higher in ASA-sensitive than in ASA-resistant platelets but there were no differences in the platelet expression of nitric oxide synthase 2 (NOS2) isoform. The highest NOS3 expression in ASA-sensitive platelets was independent of the presence of T-to-C mutation at nucleotide position -786 (T(-786) → C) in the NOS3-coding gene. However, platelet content of phosphorylated NOS3 at Serine (Ser)(1177), an active form of NOS3, was higher in ASA-sensitive than in ASA-resistant platelets. The level of platelet NOS3 Ser(1177) phosphorylation was positively associated with the closure time in the PFA-100 test. In vitro, collagen failed to stimulate the aggregation of ASA-sensitive platelets, determined by lumiaggregometry, and it was associated with a significant increase (p = 0.018) of NOS3 phosphorylation at Ser(1177). On the contrary, collagen stimulated the aggregation of ASA-resistant platelets but did not significantly modify the platelet content of phosphorylated NOS3 Ser(1177). During collagen stimulation the release of NO from ASA-sensitive platelets was significantly enhanced but it was not modified in ASA-resistant platelets.Conclusions: Functional platelet responsiveness to ASA was associated with the platelet content of phosphorylated NOS3 at Ser(1177).
PB Public Library of Science
SN 1932-6203
YR 2013
FD 2013-10-24
LK https://hdl.handle.net/20.500.14352/99275
UL https://hdl.handle.net/20.500.14352/99275
LA eng
NO Modrego J, Azcona L, Martı ́n-Palacios N, Zamorano-Leo ́n JJ, Segura A, et al. (2013) Platelet Content of Nitric Oxide Synthase 3 Phosphorylated AtSerine1177Is Associated with the Functional Response of Platelets to Aspirin. PLoS ONE 8(12): e82574. doi:10.1371/journal.pone.0082574
NO Instituto de Salud Carlos III
NO Unión Europea
DS Docta Complutense
RD 6 abr 2025