Enhanced mTORC1 Signaling in Inflammatory Monocytes Links Systemic Inflammation to Cardiovascular Disease in...

Area of Science:

• Immunology
• Cardiovascular Medicine
• Rheumatology

Background:

• Cardiovascular disease (CVD) is the primary cause of death in rheumatoid arthritis (RA) patients.
• Traditional risk factors and RA disease activity alone do not fully explain this increased CVD risk.

Purpose of the Study:

• To investigate the association between monocyte subsets, inflammatory cytokines, and mTORC signaling in RA patients with and without CVD.
• To explore potential mechanisms linking RA, inflammation, and cardiovascular comorbidity.

Main Methods:

• Flow cytometry analysis of peripheral blood mononuclear cells from RA patients with CVD, RA patients without CVD, and healthy controls.
• Classification of monocyte subsets into inflammatory (CD14+HLA-DR+CCR2+) and non-inflammatory (CD14+CD163+CCR2-) types.
• Assessment of intracellular Interleukin 1 beta (IL-1β), Interleukin 6 (IL-6), and Mammalian Target of Rapamycin Complex (mTORC) activation via S6 Ribosomal Protein phosphorylation (S6Rp).

Main Results:

• RA patients with CVD (RA-CVD+) had higher frequencies of inflammatory monocytes and elevated IL-1β and IL-6 levels compared to RA patients without CVD (RA-CVD-) and healthy controls.
• Increased mTORC activation (S6Rp phosphorylation) was observed in inflammatory monocytes of RA-CVD+ patients.
• S6Rp levels correlated with IL-1β and IL-6 in the RA-CVD+ group, but not with RA disease activity or duration.

Conclusions:

• mTORC1 signaling is elevated in inflammatory monocytes of RA patients with CVD.
• Increased mTORC activity in inflammatory monocytes may be linked to cardiovascular comorbidity in RA.
• These inflammatory monocyte alterations are independent of RA disease activity and duration.