Session Information
Date: Monday, November 13, 2023
Title: (1264–1307) RA – Diagnosis, Manifestations, and Outcomes Poster II
Session Type: Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: High-density lipoprotein (HDL) has well-characterized anti-atherogenic cholesterol efflux and antioxidant functions. Another function of HDL uncharacterized in RA is its ability to transport microRNAs (miRNAs) between cells and thus alter cellular function. The study’s purpose was to determine if HDL-miRNA cargo is altered and affects inflammation in RA.
Methods: HDL-miRNAs were characterized in 30 RA and 30 control subjects by next generation sequencing and quantitative PCR. The most abundant differentially expressed miRNA was evaluated further. The function of miR-1246 was assessed by miRNA mimics, antagomiRs, siRNA knockdown and luciferase assays. Monocyte-derived macrophages were treated with miR-1246-loaded HDL, and unmodified HDL from RA and control subjects to measure delivery of miR-1246 and its effect on IL-6.
Results: The most abundant miRNA on HDL was miR-1246; it was significantly enriched 2-fold on HDL from RA versus control subjects. HDL-mediated miR-1246 delivery to macrophages significantly increased IL6 expression 43-fold. miR-1246 delivery significantly decreased DUSP3 1.5-fold and DUSP3 siRNA knockdown increased macrophage IL6 expression. Luciferase assay indicated DUSP3 is a direct target of miR-1246. Unmodified HDL from RA delivered 1.6-fold more miR-1246 versus control subject HDL. Unmodified HDL from both RA and control subjects attenuated activated macrophage IL6 expression, but this effect was significantly blunted in RA so that IL6 expression was 3.4-fold higher after RA versus control HDL treatment.
Conclusion: HDL-miR-1246 was increased in RA versus control subjects 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.
To cite this abstract in AMA style:
Wu Q, Sheng Q, Michell D, Ramirez-Solano M, Posey O, Phothisane A, Shaik S, Vickers K, Ormseth M. The Anti-inflammatory Effect of High-density Lipoprotein Is Blunted by Delivery of Altered MicroRNA Cargo to Macrophages in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/the-anti-inflammatory-effect-of-high-density-lipoprotein-is-blunted-by-delivery-of-altered-microrna-cargo-to-macrophages-in-patients-with-rheumatoid-arthritis/. Accessed .« Back to ACR Convergence 2023
ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-anti-inflammatory-effect-of-high-density-lipoprotein-is-blunted-by-delivery-of-altered-microrna-cargo-to-macrophages-in-patients-with-rheumatoid-arthritis/