Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients.

Autor: Bertinat R; Centro de Microscopía Avanzada, CMA-BIO BIO, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile., Villalobos-Labra R; Department of Obstetrics and Gynecology, Heritage Medical Research Centre (HMRC), University of Alberta, Edmonton, Canada., Hofmann L; Institute of Biomedical Science, Department of Health Studies, FH Joanneum University of Applied Sciences, Graz, Austria., Blauensteiner J; Institute of Biomedical Science, Department of Health Studies, FH Joanneum University of Applied Sciences, Graz, Austria., Sepúlveda N; Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland; CEAUL - Centro de Estatística e Aplicações da Universidade de Lisboa, Portugal., Westermeier F; Institute of Biomedical Science, Department of Health Studies, FH Joanneum University of Applied Sciences, Graz, Austria; Centro Integrativo de Biología y Química Aplicada (CIBQA), Universidad Bernardo O'Higgins, Santiago, Chile. Electronic address: francisco.westermeier@fh-joanneum.at.
Jazyk: angličtina
Zdroj: Vascular pharmacology [Vascul Pharmacol] 2022 Apr; Vol. 143, pp. 106953. Date of Electronic Publication: 2022 Jan 21.
DOI: 10.1016/j.vph.2022.106953
Abstrakt: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by severe and persistent fatigue. Along with clinical studies showing endothelial dysfunction (ED) in a subset of ME/CFS patients, we have recently reported altered ED-related microRNAs in plasma from affected individuals. Inadequate nitric oxide (NO), mainly produced by the endothelial isoform of nitric oxide synthase (eNOS) in endothelial cells (ECs), is a major cause of ED. In this study, we hypothesized that plasma from that cohort of ME/CFS patients induces eNOS-related ED in vitro. To test this, we cultured human umbilical vein endothelial cells (HUVECs) in the presence of plasma from either ME/CFS patients (ME/CFS-plasma, n = 11) or healthy controls (HC-plasma, n = 12). Then, we measured the NO production in the absence and presence of tyrosine kinase and G protein-coupled receptors agonists (TKRs and GPCRs, respectively), well-known to activate eNOS in ECs. Our data showed that HUVECs incubated with ME/CFS-plasma produced less NO either in the absence or presence of eNOS activators compared to ones in presence of HC-plasma. Also, the NO production elicited by bradykinin, histamine, and acetylcholine (GPCRs agonists) was more affected than the one triggered by insulin (TKR agonist). Finally, inhibitory eNOS phosphorylation at Thr 495 was higher in HUVECs treated with ME/CFS-plasma compared to the same treatment with HC-plasma. In conclusion, this study in vitro shows a decreased NO production in HUVECs exposed to plasma from ME/CFS patients, suggesting an unreported role of eNOS in the pathophysiology of this disease.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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