Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients, by R Bertinat, RVillalobos-Labra, L Hofmann, J Blauensteiner, N Sepúlveda, F Westermeir in Vascular Pharmacology 2022, 106953 [doi.org/10.1016/j.vph.2022.106953]
Highlights
- ME/CFS-plasma reduced the ability of ECs to produce NO.
- Decreased NO production was linked to higher inhibitory phosphorylation of eNOS at Thr495 at the basal state.
- We provide new methodological approaches to study in vitro ED in ME/CFS.
Abstract
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.
Endothelial dysfunction is a type of non-obstructive coronary artery disease (CAD) in which there are no heart artery blockages, but the large blood vessels on the heart’s surface constrict (narrow) instead of dilating (opening). [Stanford]
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 either plasma from ME/CFS patients (ME/CFS-plasma, n = 11) or healthy controls (HC-plasma, n = 12). Then, we measured the NO production in the absence or presence of tyrosine kinase and G protein-coupled receptors agonists (TKRs and GPCRs, respectively), well-known to activate eNOS in ECs.
Our data show 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 Thr495 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.
Francisco Westermeier says on twitter:
In summary, we expect that our study can:
(1) Provide new perspectives to study endothelial function in ME/CFS.
(2) Improve the diagnosis and stratification of the subset of patients affected by endothelial dysfunction.
Comment on previous research into endothelial dysfunction:
MEA Research Review: Altered Endothelial Function in ME/CFS Blood Plasma
Discussion of results:
ME Research UK: Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients
Cure ME: Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients
