Biochim Biophys Acta Mol Cell Biol Lipids. 2026 Sep 19:159771. doi: 10.1016/j.bbalip.2026.159771. Online ahead of print.
ABSTRACT
Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease. Although it is known that metabolic disturbances alter macrophage metabolism, inflammatory responses and the ability to maintain immune homeostasis, these changes have not been well studied out of the context of atherosclerosis. Our aim was to investigate the effect of dyslipidemia caused by ApoE deficiency on macrophages and on antigen-induced arthritis in mice. Toward this aim, mice deficient in the ApoE gene were used which exhibit high total cholesterol (TC) levels distributed primarily in VLDL/IDL fractions, normal triglycerides and low HDL-C levels associated with distribution at lower densities and lower PON-1 activity. ApoE KO peritoneal macrophages had an M1-like polarization and an increased respiration rate. Importantly, ApoE KO mice developed more severe knee joint swelling compared to control mice. At the end of the arthritis protocol, spleen macrophages had increased expression of M1 cell surface markers. Simvastatin treatment reduced serum TC, increased HDL-C and PON-1 activity and improved HDL density. Additionally, treatment of ApoE KO mice with simvastatin limited the M1-associated cell surface markers on spleen macrophages and reduced arthritic joint swelling. Collectively, our findings support further investigation of lipid-modifying strategies in the context of inflammatory arthritis associated with dyslipidemia.
PMID:42762863 | DOI:10.1016/j.bbalip.2026.159771