Modulation of the activation of endothelial nitric oxide synthase and nitrosative stress biomarkers by aspirin triggered lipoxins: A possible mechanism of action of aspirin in the antiphospholipid syndrome.

Autor: Granada-Gómez M; Grupo Reproducción, Facultad de Medicina, Dpto. Microbiología y Parasitología, Universidad de Antioquia UdeA, Medellín, Colombia., Velásquez-Berrío M; Grupo Reproducción, Facultad de Medicina, Dpto. Microbiología y Parasitología, Universidad de Antioquia UdeA, Medellín, Colombia., Molina CR; Grupo de Investigación en Trombosis, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia., Martín SS; Biomedical Research Center School of Medicine, Universidad de Valparaiso, Valparaiso, Chile.; Group of Research and Innovation in Vascular Health (GRIVAS Health), Chillan, Chile., Escudero C; Vascular Physiology Laboratory, Basic Sciences Department, Faculty of Sciences, Universidad del Bio-Bio, Chillán, Chile.; Group of Research and Innovation in Vascular Health (GRIVAS Health), Chillan, Chile.; Red Iberoamericana de Alteraciones Vasculares Asociadas a TRanstornos del EMbarazo (RIVATREM)., Alvarez AM; Grupo Reproducción, Facultad de Medicina, Dpto. Microbiología y Parasitología, Universidad de Antioquia UdeA, Medellín, Colombia., Cadavid AP; Grupo Reproducción, Facultad de Medicina, Dpto. Microbiología y Parasitología, Universidad de Antioquia UdeA, Medellín, Colombia.; Grupo de Investigación en Trombosis, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia.; Red Iberoamericana de Alteraciones Vasculares Asociadas a TRanstornos del EMbarazo (RIVATREM).
Jazyk: angličtina
Zdroj: American journal of reproductive immunology (New York, N.Y. : 1989) [Am J Reprod Immunol] 2023 Aug; Vol. 90 (2), pp. e13753.
DOI: 10.1111/aji.13753
Abstrakt: Problem: Antiphospholipid syndrome (APS) is characterized by the clinical manifestation of vascular thrombosis (VT) or pregnancy morbidity (PM) and antiphospholipid antibodies (aPL) that can modify the nitric oxide production. Low-dose aspirin is used in the prevention and treatment of diverse alterations of pregnancy. One of the mechanisms of action of aspirin is to induce the production of aspirin-triggered-lipoxins (ATL). The aim of this study was to evaluate the modulatory effect of ATL over the activation of endothelial nitric oxide synthase (eNOS) and nitrosative stress biomarkers induced by aPL.
Methods: We used polyclonal IgG and sera from women with aPL and PM/VT or VT only, and from women with PM only and positive for non-criteria aPL (SN-OAPS). In these sera, biomarkers of nitrosative stress (nitrites and nitrotyrosine) were measured. The protein expression of nitrotyrosine and the phosphorylation of eNOS (at Ser1177) were estimated in human umbilical vein endothelial cells (HUVECs) stimulated with polyclonal IgG with or without ATL.
Results: Women with SN-OAPS showed increased circulating levels of nitrites and nitrotyrosine. Likewise, polyclonal IgG from either SN-OAPS or VT patients stimulated nitrotyrosine expression in HUVECs. ATL decreased the nitrotyrosine expression induced by polyclonal IgG from the SN-OAPS group. ATL also recovered the reduced eNOS phosphorylation at Ser1177 in HUVECs stimulated with polyclonal IgG from women with PM/VT or SN-OAPS.
Conclusions: Increased nitrosative stress present in serum of women with SN-OAPS is associated with IgG-mediated impaired endothelial NO synthesis in endothelial cells. ATL prevent these cellular changes.
(© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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