APOL1 Variant-Expressing Endothelial Cells Exhibit Autophagic Dysfunction and Mitochondrial Stress

Apolipoprotein L1 (APOL1) gene risk variants (RV) associate with renal and cardiovascular disease particularly in SLE. We hypothesized that in RV-carrying human umbilical vein endothelial cells (HUVECs) cytokine-induced APOL1 expression compromises mitochondrial respiration, lysosome integrity, and autophagic flux. HUVEC cultures of each APOL1 genotype were generated. APOL1 was expressed using IFN?; HUVEC mitochondrial function , lysosome integrity, and autophagic flux were measured. IFN? increased APOL1 expression across all genotypes 20-fold (p=0.001). Compared to the homozygous G0 (ancestral) allele (0RV), high risk (2RV) HUVECs showed both depressed baseline and maximum mitochondrial oxygen consumption (p