Therapeutic Potential of L- arginine in Gestational Hypertension Mouse Model Induced by sFlt-1 Overexpressing Human Adipose Tissue-Derived Mesenchymal Stem Cells.

초록

Introduction: Endothelial dysfunction plays a crucial role in the development of preeclampsia, and a low nitric oxide bioavailability is a signifcant contributing factor. Nitric oxide synthase synthesizes NO using L-arginine as a precursor. Some studies have suggested that L-arginine increases NOS levels, potentially serving as a therapeutic option for preeclampsia. However, the mechanisms and preclinical efcacy of this approach require further evaluation. This study aimed to assess the efect of arginine on blood pressure in a novel mouse model of preeclampsia using sFlt-1 overexpressing human adipose tissue-derived mesenchymal stem cells (sFlt-1 hATMSCs). Methods: sFlt-1 hATMSCs were generated by virus infection with lentiviral expression vector, constructed by inserting the sFlt-1 gene. Pregnant CD-1 mice were randomly administered intraperitoneal injection with sFlt-1 overexpressing hATMSCs (1x106 cells) on day 8 of gestation. Thereafter, the mice received L-arginine (21 mg/kg/d). On gestational day 18, the blood pressure of the mice was measured and various angiogenic molecules were assessed in their serum. Results: Intraperitoneal injection of sFlt-1 overexpressing hATMSCs using a lentiviral expression vector system resulted in a signifcant elevation in blood pressure, a signifcant increase in plasma sFlt-1, and a decrease in plasma VEGF. Moreover, L-arginine treatment signifcantly alleviated the elevated mean blood pressure in our newly developed preeclampsia mouse model. Additionally, L-arginine clearly afected other preeclampsia-associated changes, such as plasma sFlt-1 and sEng. Conclusion: Our fndings indicate that the administration of L-arginine results in a decrease in blood pressure in a mouse model of preeclampsia, implicating a therapeutic potential of L-arginine. However, additional investigations are required to understand the specifc mechanisms by which L-arginine infuences preeclampsia.