SENP3 attenuates foam cell formation by deSUMOylating NLRP3 in macrophages stimulated with ox-LDL

SUMO-specific protease 3 (SENP3) participates in the removal of SUMOylation and maintains the balance of the SUMO system, which ensures normal functioning of substrates and cellular activities. In the present study, we found that SENP3 expression was significantly reduced in ox-LDL-stimulated macrophages. SENP3 overexpression suppressed and SENP3 knockdown promoted macrophage foam cell formation. Moreover, SENP3 inhibited cholesterol uptake, CD36 expression, and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome activation in ox-LDL-stimulated macrophages. Ox-LDL-stimulated NLRP3 SUMOylation was reduced by SENP3. Blocking NLRP3 SUMOylation inhibited foam cell formation and NLRP3 inflammasome activation. Thus, this study revealed that SENP3 inhibits macrophage foam cell formation by deSUMOylating NLRP3 and regulating NLRP3 inflammasome activation, which may provide a potentially innovative approach to treatment of atherosclerosis.