| Autor: |
Gatto M; Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy., Esposito M; Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy., Morelli M; Department of Gynecology and Obstetrics, Hospital SS Annunziata, 87100 Cosenza, Italy., De Rose S; Department of Gynecology and Obstetrics, Hospital SS Annunziata, 87100 Cosenza, Italy., Gizurarson S; Faculty of Pharmaceutical Sciences, University of Iceland, 101 Reykjavik, Iceland., Meiri H; Hylabs Ltd., Rehovot 7670606, Israel.; TeleMarpe Ltd., Tel Aviv 6908742, Israel., Mandalà M; Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy.; Department of Obstetrics, Gynecology and Reproductive Sciences, Larner College of Medicine, University of Vermont, Burlington, VT 05401, USA. |
| Abstrakt: |
Placental protein 13 (PP13) exhibits a plasma concentration that increases gradually during normal gestation, a process that is disrupted in preeclampsia, which is characterized by elevated vascular resistance, reduced utero-placental blood flow, and intrauterine growth restriction. This study investigated PP13's role in vascular tone regulation and its molecular mechanisms. Uterine and subcutaneous arteries, isolated from both pregnant and non-pregnant women, were precontracted with the thromboxane analogue U46619 and exposed to PP13 using pressurized myography. The molecular mechanisms were further investigated, using specific inhibitors for nitric oxide synthase (L-NAME+LNNA at 10 -4 M) and guanylate cyclase (ODQ at 10 -5 M). The results showed that PP13 induced vasodilation in uterine arteries, but not in subcutaneous arteries. Additionally, PP13 counteracted U46619-induced vasoconstriction, which is particularly pronounced in pregnancy. Further investigation revealed that PP13's mechanism of action is dependent on the activation of the nitric oxide-cGMP pathway. This study provides novel insights into the vasomodulatory effects of PP13 on human uterine arteries, underscoring its potential role in regulating utero-placental blood flow. These findings suggest that PP13 may be a promising candidate for improving utero-placental blood flow in conditions such as preeclampsia. Further research and clinical studies are warranted to validate PP13's efficacy and safety as a therapeutic agent for managing preeclampsia. |
