Intracellular accumulation of free cholesterol in macrophages triggers a PARP1 response to DNA damage and PARP1 impairs lipopolysaccharide-induced inflammatory response.

ABSTRACT: The formation of macrophage (Mφ) foam cells is a hallmark of atherosclerosis, yet how the process of lipid loading can modulate Mφ inflammatory responses by rewiring their intracellular metabolic circuits is not well understood. Our previous studies have shown that the accumulation of oxidized LDL (oxLDL) or free cholesterol in Mφs impaired their inflammatory response by suppressing HIF-1α-mediated glycolysis and upregulating NRF2 antioxidative response. However, it remains unclear if other metabolic processes are also contributory. In this study, we found that the accumulation of free cholesterol, but not oxLDL, in primary murine thioglycolate-elicited peritoneal Mφs (PMφs) enhanced a PARP1-dependent response associated with repair of DNA damage, which was characterized by poly ADP-ribosy

SUBMITTER: Ting KKY 

PROVIDER: S-EPMC11882048 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature