Serum from Stroke Patients with High-Grade Carotid Stenosis Promotes Cyclooxygenase-Dependent Endothelial Dysfunction in Non-ischemic Mice Carotid Arteries
Puertas Umbert, Lídia (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Puig Grifol, Núria (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Camacho, Mercedes (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Dantas, Ana Paula (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Marín, Rebeca (Institut de Recerca Sant Pau)
Martí-Fàbregas, Joan (Institut de Recerca Sant Pau)
Jiménez Xarrié, Elena (Institut de Recerca Sant Pau)
Benitez, Sonia (Instituto de Salud Carlos III)
Camps-Renom, Pol (Institut de Recerca Sant Pau)
Jiménez Altayó, Francesc (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data:	2024
Resum:	Atherosclerosis is responsible for 20% of ischemic strokes, and severe carotid stenosis is associated with a higher incidence of first-ever and recurrent strokes. The release of pro-inflammatory mediators into the blood in severe atherosclerosis may aggravate endothelial dysfunction after stroke contributing to impair disease outcomes. We hypothesize that environments of severe carotid atherosclerotic disease worsen endothelial dysfunction in stroke linked to enhanced risk of further cerebrovascular events. We mounted nonischemic common carotid arteries from 2- to 4-month-old male Oncins France 1 mice in tissue baths for isometric contraction force measurements and exposed them to serum from men with a recent ischemic stroke and different degrees of carotid stenosis: low- or moderate-grade stenosis (LMGS; < 70%) and high-grade stenosis (HGS; ≥ 70%). The results show that serum from stroke patients induced an impairment of acetylcholine relaxations in mice carotid arteries indicative of endothelium dysfunction. This effect was more pronounced after incubation with serum from patients with a recurrent stroke or vascular death within 1 year of follow-up. When patients were stratified according to the degree of stenosis, serum from HGS patients induced more pronounced carotid artery endothelial dysfunction, an effect that was associated with enhanced circulating levels of IL-1β. Mechanistically, endothelial dysfunction was prevented by both nonselective and selective COX blockade. Altogether, the present findings add knowledge on the understanding of the mechanisms involved in the increased risk of stroke in atherosclerosis and suggest that targeting COX in the carotid artery wall may represent a potential novel therapeutic strategy for secondary stroke prevention.
Ajuts:	Instituto de Salud Carlos III FIS20/00252 Agencia Estatal de Investigación PID2020-113634RB-C22
Nota:	SANTPAU_2024
Nota:	Open Access Funding provided by Universitat Autonoma de Barcelona. This work was supported by Fundació La Marató de TV3[201716-10]Generalitat de Catalunya (2017-SGR-645), and Ministerio de Ciencia e Innovación (PID 2020-113634RB-C22). NP is funded by Instituto de Salud Carlos III predoctoral contract (FIS20/00252). SB is part of CIBER-Consorcio Centro de Investigación Biomédica en Red (CIBERDEM, CB07/08/0016), Instituto de Salud Carlos III.
Drets:	Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Translational Stroke Research, Vol. 15 Núm. 1 (february 2024) , p. 140-152, ISSN 1868-601X

DOI: 10.1007/s12975-022-01117-1
PMID: 36536168

13 p, 1.0 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats