Profile of circulating microRNAs in myalgic encephalomyelitis and their relation to symptom severity, and disease pathophysiology

Nepotchatykh, Evguenia; Elremaly, Wesam; Caraus, Iurie; Godbout, Christian; Leveau, Corinne; Chalder, Lynda; Beaudin, Catherine; Kanamaru, Emi; Kosovskaia, Renata; Lauzon, Shawn; Maillet, Yanick; Franco, Anita; Lascau-Coman, V.; Bouhanik, Saadallah; Gaitan, Yaned Patricia; Li, Dawei; Moreau, Alain

doi:10.1038/s41598-020-76438-y

Cited by 28 publications

(52 citation statements)

References 60 publications

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“…Microarray analyses have identified several miRs differentially expressed in ME/CFS patients compared to HCs, also supporting by in silico analyses that inflammation-related processes and immune abnormalities play a role in its pathophysiology 14 . Then, we compared the expression of miR-21, miR-34a, miR-92a, miR-126, and miR-200c in plasma samples from ME/CFSmm and ME/CFSsa versus HCs, obtained from the UKMEB 41 .…”

Section: Discussionsupporting

confidence: 52%

“…Sirt1 is another key modulator of endothelial homeostasis by activating eNOS to promote endothelium-dependent vasodilatation 11 , whose expression/activity is reduced during inflammation 10 . Over the last years, miRs have emerged as interesting candidates to identify biomarkers in ME/CFS [13][14][15][16][17] , since these noncoding RNAs play widespread roles in regulating gene expression 12 .…”

Section: Discussionmentioning

confidence: 99%

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Altered endothelial dysfunction-related miRs in plasma from ME/CFS patients

Blauensteiner

Bertinat

León

et al. 2021

Sci Rep

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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.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Altered endothelial dysfunction-related miRs in plasma from ME/CFS patients

Blauensteiner

Bertinat

León

et al. 2021

Sci Rep

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“…Nepotchatykh et al demonstrated that hsa-miR-127-3p could regulate the expression of the BCL6 gene and subsequently inhibit the expression of IL-10. This cytokine has anti-inflammatory properties and plays a central role in limiting host immune responses to pathogens [28].…”

Section: Mirnas Against Covid-19mentioning

confidence: 99%

The Role of miRNAs in COVID-19 Disease

et al. 2021

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Nowadays, the SARS Coronavirus 2 (SARS-CoV-2) infection is recognized as the primary cause of mortality in humans. SARS-CoV-2 is transmitted through human-to-human contact and is asymptomatic in most patients. In addition to approved vaccines against SARS-CoV-2 infection, miRNAs may also be promising options against this new virus. miRNAs are small and noncoding RNAs 18–25 nucleotides in length that target the mRNAs to degrade them or obstruct their translation miRNAs act as an observer in cells. This study reviewed the literature on the potential role of cellular miRNAs in the SARS-CoV-2-host interplay as a therapeutic option in COVID-19 patients.

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“…Several noncoding RNAs targeting vascular and muscular function were found dysregulated in ME/CFS suggesting an important role in their regulation [ 16 , 49 , 85 ]. A recent study showed different miRNA signatures in response to PEM induction allowing classification of ME/CFS patients into four clusters associated with symptom severity [ 85 ].…”

Section: Discussionmentioning

confidence: 99%

Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Wirth¹,

Scheibenbogen

2021

J Transl Med

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Chronic Fatigue Syndrome or Myalgic Encephaloymelitis (ME/CFS) is a frequent debilitating disease with an enigmatic etiology. The finding of autoantibodies against ß2-adrenergic receptors (ß2AdR) prompted us to hypothesize that ß2AdR dysfunction is of critical importance in the pathophysiology of ME/CFS. Our hypothesis published previously considers ME/CFS as a disease caused by a dysfunctional autonomic nervous system (ANS) system: sympathetic overactivity in the presence of vascular dysregulation by ß2AdR dysfunction causes predominance of vasoconstrictor influences in brain and skeletal muscles, which in the latter is opposed by the metabolically stimulated release of endogenous vasodilators (functional sympatholysis). An enigmatic bioenergetic disturbance in skeletal muscle strongly contributes to this release. Excessive generation of these vasodilators with algesic properties and spillover into the systemic circulation could explain hypovolemia, suppression of renin (paradoxon) and the enigmatic symptoms. In this hypothesis paper the mechanisms underlying the energetic disturbance in muscles will be explained and merged with the first hypothesis. The key information is that ß2AdR also stimulates the Na+/K+-ATPase in skeletal muscles. Appropriate muscular perfusion as well as function of the Na+/K+-ATPase determine muscle fatigability. We presume that dysfunction of the ß2AdR also leads to an insufficient stimulation of the Na+/K+-ATPase causing sodium overload which reverses the transport direction of the sodium-calcium exchanger (NCX) to import calcium instead of exporting it as is also known from the ischemia–reperfusion paradigm. The ensuing calcium overload affects the mitochondria, cytoplasmatic metabolism and the endothelium which further worsens the energetic situation (vicious circle) to explain postexertional malaise, exercise intolerance and chronification. Reduced Na+/K+-ATPase activity is not the only cause for cellular sodium loading. In poor energetic situations increased proton production raises intracellular sodium via sodium-proton-exchanger subtype-1 (NHE1), the most important proton-extruder in skeletal muscle. Finally, sodium overload is due to diminished sodium outward transport and enhanced cellular sodium loading. As soon as this disturbance would have occurred in a severe manner the threshold for re-induction would be strongly lowered, mainly due to an upregulated NHE1, so that it could repeat at low levels of exercise, even by activities of everyday life, re-inducing mitochondrial, metabolic and vascular dysfunction to perpetuate the disease.

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Profile of circulating microRNAs in myalgic encephalomyelitis and their relation to symptom severity, and disease pathophysiology

Cited by 28 publications

References 60 publications

Altered endothelial dysfunction-related miRs in plasma from ME/CFS patients

Altered endothelial dysfunction-related miRs in plasma from ME/CFS patients

The Role of miRNAs in COVID-19 Disease

Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

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