Browsing by Author "Contreras-Duarte, S."

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    High total cholesterol and triglycerides levels increase arginases metabolism, impairing nitric oxide signaling and worsening fetoplacental endothelial dysfunction in gestational diabetes mellitus pregnancies
    (2021) Contreras-Duarte, S.; Cantin, C.; Farias, M.; Leiva, A.
    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 hCatl 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.
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    Sitagliptina, un inhibidor de la enzima DPP-IV, aumenta el colesterol plasmático total, altera el perfil de colesterol lipoproteico y disminuye el transporte reverso de colesterol en ratones
    (2010) Leiva, A.; Varas, P.; Amigo, L.; Contreras-Duarte, S.; Maíz, A.; Rigotti Rivera, Attilio
    Background: Insulin and glucagon regúlate the expression of key lipoprotein metabolism enzymes. Dyslipidemia is a significant risk factor for cardiovascular disease, the main cause of death in diabetic patients. Sitagliptine, an inhibitor of type IV dipep-tidil-peptidase (DPP-IV), controlling the metabolism of incretins, is a new hypoglycemic agent used for treatment of type II diabetes. Its effects on lipid metabolism are not clearly defined. Aim: to study the effects of sitagliptine upon parameters of cholesterol metabolism in mice. Methods: C5BL6/J mice were assigned to receive ei-ther a standard diet or one with sitagliptine supplemen-tation (0.6% P/P) for 8 weeks. DPP-IV plasma, total and lipoprotein cholesterol were measured using enzyme methods. Reverse cholesterol transport was evaluated through the peritoneal injection of cholesterol loaded macrophages followed by measurement of plasma and fecall4C labeled cholesterol. Results: compared to controls, sitagliptine treated mice exhibited a 38% decrease in plasma DPP-IV Total plasma cholesterol increased by 60% with a marked increase in HDL cholesterol. Also, an increased HDL cholesterol recovered from plasma along with a 30% decrease in fecal cholesterol was observed Finally, sitagliptine admi-nistration was associated to a decreased LDL and SR-BI hepatic receptors. Conclusión: Sitagliptine administration is associated to increased levéis of plasma cholesterol, mainly the HDL fraction, and decreased reverse cholesterol transport and fecal excretion. This effects seem to be mediated by a decreased expression of SR-BI in the liver. The expected increase in atherosclerosis associated to the atherogenic changes induced by sitagliptine should be the subject for further studies in mice.