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Placental protein 13 (PP13) stimulates rat uterine vessels after slow subcutaneous administration

Placental protein 13 (PP13) stimulates rat uterine vessels after slow subcutaneous administration

Title: Placental protein 13 (PP13) stimulates rat uterine vessels after slow subcutaneous administration
Author: Drobnjak, Tijana
Jónsdóttir, Anna Margrét
Helgadottir, Helga   orcid.org/0000-0002-5422-1947
Runólfsdóttir, Margrét Soffía
Meiri, Hamutal
Sammar, Marei
Osol, George J.
Mandalà, Maurizio   orcid.org/0000-0003-3736-0205
Huppertz, Berthold   orcid.org/0000-0003-4814-2158
Gizurarson, Sveinbjorn   orcid.org/0000-0001-7824-9752
Date: 2019-03-27
Language: English
Scope: 213-222
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Lyfjafræðideild (HÍ)
Faculty of Pharmaceutical Sciences (UI)
Series: International Journal of Women's Health;2019(11)
ISSN: 1179-1411
DOI: 10.2147/IJWH.S188303
Subject: Biomarkers; ENOS; Galectins; Hypertension; LGALS13; Placenta; Preeclampsia; Pregnancy; Rat vascular system; Slow release; Meðganga; Fylgja; Háþrýstingur; Krampi; Lyfjagerð; Lyfhrifafræði
URI: https://hdl.handle.net/20.500.11815/2042

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Drobnjak T, Jónsdóttir AM, Helgadóttir H, Runólfsdóttir MS, Meiri H, Sammar M, Osol G, Mandalà M, Huppertz B, Gizurarson S. Placental protein 13 (PP13) stimulates rat uterine vessels after slow subcutaneous administration. Int J Womens Health. 2019;11:213-222 https://doi.org/10.2147/IJWH.S188303


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.


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