Figure 1: Lp(a) Uptake Is Not Modulated by LDLR Expression in Human Fibroblasts

Flow cytometric assessment of fluorescent low-density lipoprotein (LDL) (A) and fluorescent lipoprotein(a) [Lp(a)] (D) uptake in dermal skin fibroblast isolated from 1 non–familial hypercholesterolemia (FH) (control), 1 heterozygous (He) FH, 7 receptor-defective homozygous (Ho) FH, and 4 receptor-negative HoFH patients. Cells were treated with mevastatin with or without recombinant gain-of-function proprotein convertase subtilisin kexin type 9 (PCSK9) (600 ng/ml) and/or alirocumab (19.2 μg/ml). Representative confocal microscopy images (Z stacks) of fluorescent LDL (red hot) (B) and fluorescent Lp(a) (yellow hot) (E) cellular uptake in control and HoFH fibroblasts are displayed. Nuclei are shown in blue. Relative uptake of fluorescent LDL (C) and fluorescent Lp(a) (F) in the presence of 20-fold excess unlabeled LDL and Lp(a), respectively, in fibroblasts from 1 non-FH control and 3 HoFH patients. ΔMFI is the mean fluorescence intensity difference between cells incubated with and cells incubated without fluorescent lipoproteins (i.e., autofluorescence). ΔMFI is in arbitrary units. *p < 0.001, **p < 0.03 vs. non-FH control without PCSK9 and without LDL excess, #p < 0.005 vs. non-FH control without PCSK9 and without alirocumab, using 2-way analysis of variance on rank-transformed values with post-hoc Newman-Keuls test. Histograms represent the mean ± SEM of a minimum of 3 independent experiments (except for HeFH, n = 1).