Effect of the LDL:HLM interaction on LDL-mediated PCSK9 uptake inhibition. A: Relative uptake, as measured by luminescence assay, of PCSK9-NLuc by HepG2 cells coincubated with LDL (blue), treated with heparinase (orange), or both (brown). Raw luminescence data are normalized to 1 for PCSK9-NLuc coincubation in the absence of LDL or heparinase treatment and 0 in the absence of PCSK9-NLuc. P values indicate comparison to the control arm (no treatment, red) unless otherwise indicated. B: Relative uptake, as measured by luminescence assay, of PCSK9-NLuc by HepG2 cells in the presence of either native (blue) or reductively methylated (purple) LDL, stratified by sequential addition (open bars) or preincubation (filled bars) of PCSK9 with LDL. Raw luminescence data are normalized to 1 for PCSK9-NLuc treatment in the absence of LDL and 0 in the absence of PCSK9-NLuc uptake. P values indicate comparison to the control arm (no LDL, red) unless otherwise indicated.