SPARCL1 Regulates Proliferation and Angiogenesis of HUVECs Through the DLL4/NOTCH1 Pathway in Preeclampsia.

Vascular endothelial dysfunction plays a critical role in the development of preeclampsia (PE). Secreted protein acidic and cysteine rich like 1 (SPARCL1) plays a role in regulating angiogenesis, yet its role in PE remains unclear. This study investigates the involvement of SPARCL1 in the development of PE. Placental tissues from healthy volunteers and patients with PE were collected to detect the expression of SPARCL1. Human umbilical vein endothelial cells (HUVECs) cultured under hypoxic conditions were utilized to investigate the role of SPARCL1 in PE. The biological behaviors of the cells were examined through cell functional assay. The expressions of DLL4/NOTCH1/HES1/VEGF proteins as well as apoptosis-related proteins were evaluated by western blot. The effects of SPARCL1/DLL4 on hypoxia-induced HUVECs were verified via rescue experiments. SPARCL1 was upregulated in placental tissues of PE patients and hypoxia-induced HUVECs. In hypoxia-induced HUVECs, shSPARCL1 facilitated the proliferative, migratory, invasive, and tube-forming capabilities yet inhibited apoptosis. ShSPARCL1 upregulated the protein levels of VEGF, HES1, NOTCH1 and DLL4. However, above-mentioned effects were all reversed by shDLL4. SPARCL1 may influence the proliferative, migratory, invasive, and tube-forming capabilities of hypoxia-induced HUVECs by regulating the DLL4/NOTCH1 axis, thereby facilitating the progression of PE.