Fecha de la publicación: 28/07/2020
Autor: Silvia Bleda (1), Joaquin de Haro (2), Isabel Sánchez (3), Ilsem Laime (2), Francisco Acin (2)
1Servicio de Angiología y Cirugía Vascular, Hospital Universitario de Getafe, Madrid, España. Electronic address: firstname.lastname@example.org.
2Servicio de Angiología y Cirugía Vascular, Hospital Universitario de Getafe, Madrid, España.
3Departamento de Investigación, Fundación para la investigación biomédica del Hospital Universitario de Getafe, Madrid, España.
Introduction and objectives: NRP1 inflammasome is crucial in endothelial dysfunction. Platelets are mandatory for the inflammation that precedes it. Aspirin could inhibit NLRP1 inflammasome in endothelial cells, and clopidogrel could also provoke a reduction in vascular inflammation. A study was carried out on the influence of platelet inflammatory inhibition by P2Y receptor inhibition versus COX enzyme inhibition on the transcription of NLRP1 inflammasome in endothelial cells.
Methods: An open-label, prospective, randomised crossover study with two periods of platelet inhibition enrolled 20 healthy volunteers. They received clopidogrel 75mg/day/7days and aspirin 100mg/day/7days. A venous blood sample was collected from all participants before and after this period. Human aortic endothelial cells (HAECs) were exposed for 2h in cultures. NLRP1 gene expression was then analysed in these cultures.
Results: HAEC cultures that were exposed to baseline plasma showed higher expression of NLRP1 than HAECs exposed to plasma after one week of aspirin or clopidogrel intake [relative quantification (RQ), 1.077±0.05 vs. 1.002±0.06; OR, 1.8; 95% CI, 1.1-2.9; P<.01 and 1.077±0.05 vs. 1.04±0.03; OR, 1.7; 95% CI, 1.2-2.6; P<.001, respectively]. NLRP1 expression in HAEC cultures exposed to plasma after one week of aspirin or clopidogrel was similar to that observed in control HAECs that was no exposed to human plasma (PBS) [RQ; 1.002±0.06 vs. 1.009±0.03; OR, 0.9; 95% CI, 0.5-1.4; P=.7, and 1.04±0.03 vs. 1.009±0.03; OR, 0.8; 95% CI, 0.3-1.2; P=.5, respectively]. No difference was observed in NLRP1 percentage reduction in HAEC after aspirin or clopidogrel exposure (3.8% vs. 2.8%, P=.3, respectively).
Conclusions: Platelet inhibition by P2Y pathway is similar to COX pathway in NLRP1 expression inhibition in HAECs.
Copyright © 2020 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.