Role of GRK2 in Trophoblast Necroptosis and Spiral Artery Remodeling: Implications for Preeclampsia Pathogenesis
Zi Lv, Liling Xiong, Xian Qin, Hua Zhang, Xin Luo, Wei Peng, Mark D. Kilby, Richard Saffery, Philip N. Baker, Hongbo Qi
Abstract
. These further induced preeclampsia-like phenotype in mice: hypertension, proteinuria, and elevated pro-angiogenic cytokines. By human extra-villous invasive trophoblast cell line (HTR8/SVneo cells), we revealed the knockdown or inhibition of GRK2 triggered excessive death with typical necroptotic characteristics: nuclear envelope rupture and the activation of RIPK1, RIPK3, and MLKL. Necrostatin-1, an inhibitor of RIPK1, is able to restore the survival of trophoblasts. Together, our findings demonstrated that insufficient GRK2 activity compromises spiral artery remodeling and initiates necrotic events in placentae, thereby leading to preeclampsia. These findings advance our understanding of GRK2 in the pathogenesis of preeclampsia and could shed light on a potential treatment for preeclampsia.