Sustained monocyte activation by persistent challenges with either oxLDL or free cholesterol and underlying mechanisms.

ABSTRACT: Chronic low-grade inflammation is a hallmark of atherosclerosis and cardiovascular diseases, with monocytes playing a central role in sustaining this pathological state. In this study, we demonstrate that prolonged exposure to oxidized low-density lipoprotein (oxLDL) or cholesterol reprograms murine bone marrow-derived monocytes into a persistent pro-inflammatory phenotype. This is characterized by elevated surface markers (CD49d, CD74, CD38, CD86), enhanced endothelial and T cell interactions, and sustained activation of the Src-SYK-mTORC1-STAT3/5 signaling axis. Notably, the inflammatory state persisted even after stimulus withdrawal, suggesting the establishment of an immune memory-like phenotype. Mechanistically, we defined the membrane clustering of Src is responsible for the generati

SUBMITTER: Wu Y 

PROVIDER: S-EPMC12929915 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature