Maternal physiological dyslipidemia (MPD) supports fetal development in human pregnancy. However, some women develop maternal supraphysiological dyslipidemia (MSPD: increased total cholesterol (TC) and triglycerides (TG) levels). MSPH is present in normal and also in gestational diabetes mellitus (GDM) pregnancies. MSPD and GDM associate with fetoplacental endothelial dysfunction, producing alterations in nitric oxide (NO)-L-arginine/arginase metabolism. Nevertheless, the effect of MSPD on GDM, and how this synergy alters fetoplacental endothelial function is unknown. Therefore, the aim of this study was to evaluate in human umbilical vein endothelial cells, the effects of MSPD in GDM and how these pathologies together affect the fetoplacental endothelial function. 123 women at term of pregnancy were classified as MPD (n = 40), MSPD (n = 35), GDM with normal lipids (GDM-MPD, n = 23) and with increased lipids (GDM-MSPD, n = 25). TC ≥291 mg/dL and TG ≥275 mg/dL were considered as MSPD. Endothelial NO synthase (eNOS), human cationic amino acid transporter 1 (hCat1), and arginase II protein abundance and activity, were assayed in umbilical vein endothelial cells. In MSPD and GDM-MSPD, TC and TG increased respect to MPD and GDM-MPD. eNOS activity was reduced in MSPD and GDM-MSPD, but increased in GDM-MPD compared with MPD. However, decreased tetrahydrobiopterin levels were observed in all groups compared with MPD. Increased hCat1 protein and L-arginine transport were observed in both GDM groups compared with MPD. However, the transport was higher in GDM-MSPD compared to GDM-MPD. Higher Arginase II protein and activity were observed in GDM-MSPD compared with MPD. Thus, MSPD in GDM pregnancies alters fetal endothelial function associated with NO metabolism.

母体生理血脂异常 (MPD) 支持人类怀孕期间的胎儿发育。然而，一些女性会出现母体超生理性血脂异常（MSPD：总胆固醇 (TC) 和甘油三酯 (TG) 水平升高）。MSPH 存在于正常和妊娠期糖尿病 (GDM) 妊娠中。MSPD 和 GDM 与胎盘内皮功能障碍相关，导致一氧化氮 (NO)-L-精氨酸/精氨酸酶代谢发生改变。然而，MSPD 对 GDM 的影响以及这种协同作用如何改变胎盘内皮功能尚不清楚。因此，本研究的目的是评估人脐静脉内皮细胞中 MSPD 对 GDM 的影响以及这些病理如何共同影响胎儿胎盘内皮功能。123 名足月妇女被归类为 MPD (n = 40)、MSPD (n = 35)、GDM 与正常脂质 (GDM-MPD, n = 23) 和增加的脂质 (GDM-MSPD, n = 25)。TC ≥291 mg/dL 和 TG ≥275 mg/dL 被视为 MSPD。在脐静脉内皮细胞中测定了内皮 NO 合酶 (eNOS)、人类阳离子氨基酸转运蛋白 1 (hCat1) 和精氨酸酶 II 蛋白丰度和活性。在 MSPD 和 GDM-MSPD 中，TC 和 TG 增加了对 MPD 和 GDM-MPD 的尊重。与 MPD 相比，eNOS 活性在 MSPD 和 GDM-MSPD 中降低，但在 GDM-MPD 中增加。然而，与 MPD 相比，在所有组中都观察到四氢生物蝶呤水平降低。与 MPD 相比，在两个 GDM 组中均观察到 hCat1 蛋白和 L-精氨酸转运增加。然而，与 GDM-MPD 相比，GDM-MSPD 中的传输更高。与 MPD 相比，在 GDM-MSPD 中观察到更高的精氨酸酶 II 蛋白和活性。因此，