Altered endothelial dysfunction-related miRs in plasma from ME/CFS patients, 2021, Blauensteiner et al

[InitialConditions]

https://www.nature.com/articles/s41598-021-89834-9

ABSTRACT
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by unexplained debilitating fatigue. Although the etiology is unknown, evidence supports immunological abnormalities, such as persistent inflammation and immune-cell activation, in a subset of patients. Since the interplay between inflammation and vascular alterations is well-established in other diseases, endothelial dysfunction has emerged as another player in ME/CFS pathogenesis. Endothelial nitric oxide synthase (eNOS) generates nitric oxide (NO) that maintains endothelial homeostasis. eNOS is activated by silent information regulator 1 (Sirt1), an anti-inflammatory protein. Despite its relevance, no study has addressed the Sirt1/eNOS axis in ME/CFS. The interest in circulating microRNAs (miRs) as potential biomarkers in ME/CFS has increased in recent years. Accordingly, we analyze a set of miRs reported to modulate the Sirt1/eNOS axis using plasma from ME/CFS patients.

Our results show that miR-21, miR-34a, miR-92a, miR-126, and miR-200c are jointly increased in ME/CFS patients compared to healthy controls. A similar finding was obtained when analyzing public miR data on peripheral blood mononuclear cells. Bioinformatics analysis shows that endothelial function-related signaling pathways are associated with these miRs, including oxidative stress and oxygen regulation. Interestingly, histone deacetylase 1, a protein responsible for epigenetic regulations, represented the most relevant node within the network. In conclusion, our study provides a basis to find endothelial dysfunction-related biomarkers and explore novel targets in ME/CFS.

 

[InitialConditions]

Discussion from author here:


Lots of work/findings on endothelial cells / function recently, including in POTS. I have no idea what they are / do. :-$

 

[Andy]

From the paper, for info.

"Acknowledgements

This study was supported by ME Research UK (SCI charity number SC036942) and carried out using samples from the UK ME/CFS Biobank, which were processed and stored at the UCL-RFH BioBank). The authors thank all the study participants for donating their blood to the UK ME/CFS Biobank (UKMEB) and also the ME/CFS community who raised funds to facilitate the UKMEB projects. The authors also want to thank the ME/CFS Society Austria (Österreichische Gesellschaft für ME/CFS, CFS-Hilfe), and the FH JOANNEUM University of Applied Sciences for supporting gran applications. FW thanks Mr. Mika Remes (QIAGEN) for his technical assistance. Finally, FW especially thanks Mr. Luis Westermeier for his support and encouragement throughout this study."

 

[Lindberg]

Could this have anything to do with anti-ETAR antibodies? Or would that be totally irrelevant for this matter?

 

[Hutan]

That a nice acknowledgements section. It's good to see researchers from Austria and Chile working on ME/CFS biology.

J. Blauensteiner
Institute of Biomedical Science, Department of Health Studies, FH Joanneum University of Applied Sciences, Graz, Austria

R. Bertinat
Centro de Microscopía Avanzada, CMA-BIO BIO, Facultad de Ciencias Biológica, Universidad de Concepción, Concepción, Chile

L. E. León
Instituto de Ciencias Biomédicas, Facultad de Ciencias de La Salud, Universidad Autónoma de Chile, Santiago, Chile

M. Riederer
Institute of Biomedical Science, Department of Health Studies, FH Joanneum University of Applied Sciences, Graz, Austria

N. Sepúlveda
Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
Centro de Estatística e Aplicações, Universidade de Lisboa, Lisbon, Portugal
Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität (FU) Berlin, Humboldt-Universität Zu Berlin and Berlin Institute of Health (BIH), Berlin, Germany

F. Westermeier
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

 

[Hutan]

This study - miRNA in plasma



Analysis of previously published data of miRNA in PBMCs:


There's overlap between levels in pwME and healthy controls of course, but average levels do seem to be higher and this is consistent in another study. I haven't read the paper yet, but it looks interesting.

 

[Grigor]

 

[dreampop]

Interestingly, histone deacetylase 1, a protein responsible for epigenetic regulations, represented the most relevant node within the network

Histone deacetylase has come up a few times over the past decade.

1) In 2011, Lenny Jason found, in this paper

Individuals with CFS display increased expression of HDAC 2 and 3, concomitant with decreased plasma cortisol. ► Those with CFS demonstrate lower total antioxidant power concomitant with down-regulation of the encoding gene NR3C1. ► Signaling dysregulation may exist in CFS, with increased HDAC expression along with reduced NR3C1 and cortisol expression.

2) A group at Brussels has set up a study that that will look at HDAC genes under PEM.

https://clinicaltrials.gov/ct2/show/NCT04378634

3) One of the more interesing papers, imo, of recent years was Neil McGregor's "Hypermetabolism" findings, which included blood and urine testing and indicated, amongst other things, problems with purine metabolism.

These data indicate hypoacetylation was occurring, which may also be related to deregulation ofmultiple cytoplasmic enzymes and DNA histone regulation. These findings suggest the primaryevents associated with PEM were due to hypoacetylation and metabolite loss during the acutePEM response.

This paper has identified that the post-exertional malaise experienced by an Australian Anglo-Celtic cohort of ME/CFS cases is associated with a deregulation of purine metabolism and low acetate levels.This deregulation of purine metabolism is associated with a change in glycolytic activity and a switchto urea cycle creatine phosphate energy usage [2]. This has the effect of reducing the availability ofacetate and upregulating histone deacetylase activity [4]. A four- and two-fold increase in HDAC2and HDAC3, respectively, have been confirmed in ME/CFS cases [6] and a very high level of HDAC1and HDAC2 binding sites occur within the genes upregulated in ME/CFS cases following exercise(see Table S1) [7].

 

[dreampop]

I believe there might be use in going to see if it pinged any other epigentic me/cfs studies, but I'm too tired to do that atm.