Abstract Background Numerous sex differences has been described in aterosclerosis including in endothelial dysfunction. Oxidized low-density lipoproteins (ox-LDL) contribute to the formation of atherosclerotic plaque by binding to a membrane glycoprotein expressed by endothelial cells. Ox-LDL also play a key role in mediating endothelial dysfunction during pregnancy. Elevated maternal ox-LDL levels can lead to oxidative stress, inflammation and apoptosis in placental and fetal endothelial cells. The aim of this study was to investigate sex-related differences in the response to ox-LDL-induced damage in human umbilical vein endothelial cells (HUVECs) isolated from male and female newborns. Methods In our study, the effects of 100 µg/ml ox-LDL on HUVECs, obtained from umbilical cords of healthy newborns of both sexes, were analyzed. By flow cytometry, fluorescence microscopy, and Western blotting techniques, mitochondrial function, cell survival, and autophagy were studied. Results Sex differences in cell motility and fate have been detected after ox-LDL treatment. Indeed, following ox-LDL treatment, male HUVECs (MHUVECs ) exhibited reduced motility and a significant increase in adhesion molecules ICAM-1 and VCAM-1, in contrast to female HUVECs (FHUVECs). Furthermore, MHUVECs exhibited higher levels of fission proteins (DRP1 and Fis1), superoxide anion (O₂⁻), and earlier mitochondrial membrane (MM) hyperpolarization, while FHUVECs showed higher levels of fusion proteins (OPA1 and MFN2), hydrogen peroxide (H₂O₂), and delayed MM changes. These findings were consistent with a greater propensity for apoptosis in MHUVECs. In contrast, FHUVECs exhibited higher levels of Survivin, making them less susceptible to apoptosis and more susceptible to the autophagy process. Conclusions Our findings reveal significant sex-related variations in endothelial responses to oxidative stress. The enhanced survival and repair capacity of FHUVECs suggests that female cells are more resilient to ox-LDL-induced damage.
Cittadini et al. (2026) studied this question.