The effect of TNF-α inhibitor treatment on microRNAs and endothelial function in collagen induced arthritis

Sulè Gunter, Frederic S Michel, Serena S Fourie, Mikayra Singh, Regina le Roux, Ashmeetha Manilall, Lebogang P Mokotedi, Aletta M E Millen

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Chronic inflammation causes dysregulated expression of microRNAs. Aberrant microRNA expression is associated with endothelial dysfunction. In this study we determined whether TNF-α inhibition impacted the expression of miRNA-146a-5p and miRNA-155-5p, and whether changes in the expression of these miRNAs were related to inflammation-induced changes in endothelial function in collagen-induced arthritis (CIA). Sixty-four Sprague-Dawley rats were divided into control (n = 24), CIA (n = 24) and CIA+etanercept (n = 16) groups. CIA and CIA+etanercept groups were immunized with bovine type-II collagen, emulsified in incomplete Freund's adjuvant. Upon signs of arthritis, the CIA+etanercept group received 10mg/kg of etanercept intraperitoneally, every three days. After six weeks of treatment, mesenteric artery vascular reactivity was assessed using wire-myography. Serum concentrations of TNF-α, C-reactive protein, interleukin-6, vascular adhesion molecule-1 (VCAM-1) and pentraxin-3 (PTX-3) were measured by ELISA. Relative expression of circulating miRNA-146a-5p and miRNA-155-5p were determined using RT-qPCR. Compared to controls, circulating miRNA-155-5p, VCAM-1 and PTX-3 concentrations were increased, and vessel relaxation was impaired in the CIA (all p<0.05), but not in the CIA+etanercept (all p<0.05) groups. The CIA group had greater miRNA-146a-5p expression compared to the CIA+etanercept group (p = 0.005). Independent of blood pressure, miRNA-146a-5p expression was associated with increased PTX-3 concentrations (p = 0.03), while miRNA-155-5p expression was associated with impaired vessel relaxation (p = 0.01). In conclusion, blocking circulating TNF-α impacted systemic inflammation-induced increased expression of miRNA-146a-5p and miRNA-155-5p, which were associated with endothelial inflammation and impaired endothelial dependent vasorelaxation, respectively.

Original languageEnglish
Pages (from-to)e0264558
JournalPLoS ONE
Volume17
Issue number2
DOIs
Publication statusPublished - 2022

Keywords

  • Acetylcholine/pharmacology
  • Animals
  • Antirheumatic Agents/pharmacology
  • Arthritis, Experimental/etiology
  • Biomarkers/blood
  • C-Reactive Protein/analysis
  • Cattle
  • Collagen Type II/administration & dosage
  • Etanercept/pharmacology
  • Female
  • Male
  • Mesenteric Arteries/drug effects
  • MicroRNAs/blood
  • Rats
  • Rats, Sprague-Dawley
  • Serum Amyloid P-Component/analysis
  • Tumor Necrosis Factor-alpha/blood
  • Up-Regulation/drug effects
  • Vascular Cell Adhesion Molecule-1/blood

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