Effect of DFPP on Ferroptosis in Peripheral Blood CD14 + Monocytes of Hyperlipidemic Patients Involving the ACSL4 / LPCAT3 / ALOX5 Pathway

INTRODUCTION: Hyperlipidemia is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Although statins are the cornerstone of lipid-lowering therapy, their use may be limited in some patients by adverse effects. This study evaluated the possible impact of non-drug treatment using double-filtration plasmapheresis (DFPP) on CD14+ monocytes and to identify alterations in plasma proteomics after DFPP in patients with hyperlipidemia. METHODS: Thirty-seven hyperlipidemic patients were enrolled. Mitochondria changes, lipid peroxidation, reactive oxygen species (ROS), and mitochondrial lipid peroxidation were examined. CD14+ monocyte proteins related to ferroptosis were assayed by western blotting, and plasma proteomic changes were measured by data-independent acquisition (DIA). RESULTS: In comparison to their levels prior to double-filtration plasmapheresis (DFPP), there was a notable reduction in total cholesterol (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) (Lp(a)), and small dense low-density lipoprotein cholesterol (sdLDL) after DFPP. DFPP may attenuate ferroptosis in peripheral blood CD14+ monocytes of patients with hyperlipidemia. Three protein candidates were identified from the DIA dataset. CONCLUSIONS: DFPP exerts lipid-lowering effects in patients with hyperlipidemia. The ACSL4/LPCAT3/ALOX5 pathway and the three proteins are likely involved in alleviating ferroptosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03491956.