Foam cells have been frequently used in studies related to atherosclerosis. Traditional methods for inducing oxidized low-density lipoprotein (oxLDL) involve copper ion (Cu2+) treatment, which has inherent limitations such as prolonged oxidation times and residual copper ions. This study explored high-frequency ultrasound (400 kHz) as an alternative method for LDL oxidization. The findings demonstrated that high-frequency ultrasound-oxidized LDL (U-oxLDL) exhibited no significant differences compared to copper-oxidized LDL (Cu-oxLDL) in terms of electrophoretic mobility, foam cell morphology, lipid content, and cholesterol transport proteins. Additionally, lipidomic analysis revealed that U-oxLDL was more comparable to native LDL (N-LDL). Transcriptomic profiling of bone marrow-derived macrophages (BMDMs) treated with oxLDL showed that the gene expression patterns of BMDM foam cells treated with U-oxLDL were over 90 % consistent with those treated with Cu-oxLDL. Therefore, high-frequency ultrasound oxidation method represents a green and efficient strategy for oxLDL preparation, offering potential advantages for advancing atherosclerosis research
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