Modulatory Effects of Mdivi-1 on OxLDL-Induced Metabolic Alterations, Inflammatory Responses, and Foam Cell Formation in Human Monocytes 2253928

Abstract

Abstract Introduction Atherosclerosis, a leading cause of cardiovascular disease, is characterized by lipid accumulation and chronic inflammation within arterial walls, where oxidized low-density lipoprotein (OxLDL) plays a pivotal role. OxLDL promotes monocyte differentiation into foam cells and triggers metabolic reprogramming alongside pro-inflammatory signaling, thereby accelerating disease progression. Methods This study examined the effects of Mdivi-1, a mitochondrial fission inhibitor, and S1QEL, a selective inhibitor of complex I—associated reactive oxygen species (ROS), on OxLDL-induced responses in monocytes. Primary human monocytes isolated from healthy donors were treated with OxLDL in the presence or absence of Mdivi-1 or S1QEL and analyzed for metabolic alterations, cytokine expression, foam cell formation, and ROS generation. Results OxLDL treatment enhanced glycolytic activity (ECAR), increased expression of pro-inflammatory cytokines IL1B and CXCL8, and promoted foam cell formation accompanied by elevated mitochondrial ROS (mtROS). Both Mdivi-1 and S1QEL significantly attenuated OxLDL-induced glycolytic reprogramming, cytokine expression, foam cell formation, and mtROS production. Conclusion These findings indicate that Mdivi-1 and S1QEL effectively modulate key metabolic and inflammatory responses in OxLDL-treated monocytes, highlighting their therapeutic potential in atherosclerosis. Funding Source AHA, NIA Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)