Rheumatoid arthritis

Anti‐Inflammatory Effect of High‐Density Lipoprotein Blunted by Delivery of Altered MicroRNA Cargo in Patients With Rheumatoid Arthritis

Arthritis RheumatolPublished Mechanistic study

Authors' conclusion

HDL-miR-1246 was increased in RA versus control participants and delivery of miR-1246 to macrophages increased IL-6 expression by targeting DUSP3. The altered HDL-miRNA cargo in RA blunted HDL's anti-inflammatory effect.

Study context

Population
Rheumatoid arthritis (RA) and control participants; monocyte-derived macrophages treated with miR-1246-loaded high-density lipoprotein (HDL) and unmodified HDL
Participants
30 vs 30
Comparison
HDL-miRNA cargo in RA vs control participants
  • RAn = 30
  • Controln = 30reference
Outcome
Whether HDL-miRNA cargo is altered and affects inflammation in RA
Methodological detailsnext generation sequencing, quantitative polymerase chain reaction, miRNA mimics, antagomiRs, small interfering RNA knockdown and luciferase assays
  • Next generation sequencing
  • Quantitative polymerase chain reaction
  • miRNA mimics, antagomiRs, small interfering RNA knockdown and luciferase assays

Main finding

As reported in the abstract

Most abundant miRNA on HDL
miR-1246
miR-1246 enrichment on HDL, RA vs control (significant)
two-fold
IL6 expression increase with HDL-mediated miR-1246 delivery to macrophages (significant)
43-fold
DUSP3 decrease with miR-1246 delivery (significant); DUSP3 siRNA knockdown increased macrophage IL6 expression
1.5-fold
miR-1246 delivered by unmodified HDL, RA vs control
1.6-fold more
Activated macrophage IL6 expression after RA vs control HDL treatment (HDL's attenuating effect significantly blunted in RA)
3.4-fold higher

Original publication

Anti‐Inflammatory Effect of High‐Density Lipoprotein Blunted by Delivery of Altered MicroRNA Cargo in Patients With Rheumatoid Arthritis. Arthritis Rheumatol. Published 24 January 2024. doi:10.1002/art.42782

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