Hyperglycemia in pregnancy (HIP) is linked to fetoplacental endothelial dysfunction, which might be a result of hyperglycemia. Hyperglycemia is associated with cell senescence; however, the role and mechanism of high glucose and cell senescence in HIP endothelial cell failure are largely unknown. Our study discovered that human umbilical vein endothelial cells (HUVECs) obtained from HIP pregnant women exhibit excessive senescence, with significantly elevated expression of senescence markers senescence-associated beta-galactosidase (SA-β-gal), p16, p21, and p53. Subsequently, we found that exposing primary HUVECs and cell lines to high glucose resulted in an increase in the synthesis of these senescence indicators, similar to what had been observed in pregnant women with HIP. A replicate senescence model and stress-induced premature senescence (SIPS) model showed higher amounts of vascular damage indicators, including von Willebrand factor (vWF), chemotactic C-C motif chemokine ligand 2 (CCL2), intercellular adhesion molecule 1 (ICAM-1), along with the anti-apoptotic protein BCL2. However, lower expressions of the pro-apoptotic component BAX, in addition to defective proliferation and tubulogenesis, were seen. Further studies indicated that hyperglycemia can not only induce these alterations in HUVECs but also exacerbate the aforementioned changes in both aging HUVECs. The experiments outlined above have also been validated in pregnant women with HIP. Collectively, these data suggest that exposure to high glucose accelerates cell senescence-mediated vein endothelial cell dysfunction, including excessive inflammation, cell adhesion, impaired angiogenesis, and cell proliferation possibly contributing to pregnancy complications and adverse pregnancy outcomes.
Keywords: cellular senescence; hyperglycemia; pregnancy; umbilical vein endothelial cells.