International Journal of Women's Health (Mar 2019)
Placental protein 13 (PP13) stimulates rat uterine vessels after slow subcutaneous administration
Abstract
Tijana Drobnjak,1 Anna Margrét Jónsdóttir,2 Helga Helgadóttir,1 Margrét Soffía Runólfsdóttir,1 Hamutal Meiri,3,4 Marei Sammar,5 George Osol,6 Maurizio Mandalà,7 Berthold Huppertz,8 Sveinbjörn Gizurarson1 1Faculty of Pharmaceutical Sciences, School of Health Science, University of Iceland, Reykjavik, Iceland; 2Department of Pathology, University Hospital Iceland, Reykjavik, Iceland; 3Hy Laboratories Ltd, Rehovot, Israel; 4TeleMarpe Ltd., Tel Aviv, Israel; 5Ephraim Katzir Department of Biotechnology Engineering, ORT Braude College, Karmiel, Israel; 6Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT, USA; 7Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy; 8Department of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria Introduction: Reduced concentrations of placental protein 13 (PP13) during the first trimester of human pregnancy are associated with elevated risk for the subsequent development of preeclampsia, which is one of the deadliest obstetrical complications of pregnancy. Previous studies by our group have shown that PP13 lowers blood pressure in pregnant rats, increases the size and weight of pups and placentas, and induces vasodilation of resistance arteries through endothelial signaling pathways involving endothelial nitric oxid synthase and prostaglandin. Methods: In the present study, the effect of PP13 was investigated in nonpregnant female Sprague Dawley rats (n=27). Osmotic pumps were surgically implanted subcutaneously that released a constant dose of PP13 or saline over 7 days. Most animals were sacrificed 6 days after the end of PP13 release (on day 13), while some were sacrificed immediately at the end of day 7 (the last PP13 release day), to compare the short- and long-term impact of PP13 on vessels’ growth and size. Results: The uterine vessels were significantly expanded in the group exposed to recombinant PP13 (rPP13) compared to the control (saline) group. Both veins and arteries were significantly expanded by rPP13 with a more pronounced effect after 13 days compared to the corresponding vessels after 7 days. Furthermore, the long-term effect of treatment by rPP13 was more pronounced in the veins compared to the corresponding arteries. The effect of a PP13 variant with a histidine-tag (His-PP13) remained the same between 7 and 13 days. Conclusion: In conclusion, PP13 might play a key role in the expansive remodeling of the uterine vessels, reflecting what would happen if the rat was pregnant, preparing the uterine vasculature for the increase in uteroplacental blood flow, which is necessary for normal pregnancy. We suggest that PP13 could act by NO signaling pathways, a hypothesis that requires future study. Keywords: preeclampsia, placenta, biomarkers, LGALS13, hypertension, pregnancy, rat vascular system, galectins, eNOS, slow release
