Placental protein 13 (PP13): a new biological target shifting individualized risk assessment to personalized drug design combating pre-eclampsia

Pre-eclampsia affects 2-7% of all pregnant women and is a major cause of maternal and fetal morbidity and mortality. The etiology of pre-eclampsia is still unknown but it is well documented that impaired placentation is a major contributor to its development. One of the placenta-specific proteins is...

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Bibliographic Details
Published in:Human reproduction update 2013-07, Vol.19 (4), p.391-405
Main Authors: Huppertz, Berthold, Meiri, Hamutal, Gizurarson, Sveinbjorn, Osol, George, Sammar, Marei
Format: Article
Language:English
Subjects:
Animals
Biomarkers - blood
Biomarkers - metabolism
Drug Design
Female
Galectins - blood
Galectins - metabolism
Humans
Pilot Projects
Placenta - metabolism
Placentation
Pre-Eclampsia - blood
Pre-Eclampsia - drug therapy
Pre-Eclampsia - metabolism
Precision Medicine
Pregnancy
Pregnancy Proteins - blood
Pregnancy Proteins - metabolism
Pregnancy Trimester, First
Rats
Risk Assessment
Uterine Artery
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Summary:Pre-eclampsia affects 2-7% of all pregnant women and is a major cause of maternal and fetal morbidity and mortality. The etiology of pre-eclampsia is still unknown but it is well documented that impaired placentation is a major contributor to its development. One of the placenta-specific proteins is placental protein 13 (PP13). Lower first trimester levels of maternal serum PP13 and its encoding placental mRNA are associated with the development of both early and late-onset severe pre-eclampsia. In cases where this protein is mutated, the frequency of pre-eclampsia is higher. 19 out of 68 studies on PP13, published between January 2006 and September 2012, were used to evaluate the value of maternal blood PP13 as a marker of pre-eclampsia. A meta-analysis presented in this review shows that low serum levels of PP13 in the first trimester of pregnancy can predict the development of pre-eclampsia later in pregnancy. Although some functions of this protein have been assessed in in vitro experiments, the in vivo functions of PP13 are still unknown, especially when circulating in the maternal bloodstream. A recent pilot study has shown that in gravid rats PP13 causes significant vasodilatation, reduced blood pressure and increased maternal uterine artery remodeling. Reviewing these effects of PP13, the authors propose the use of PP13 as a new drug candidate. Replenishing PP13 in those women with low serum levels early in pregnancy may help prepare their vasculature for pregnancy. This novel pharmacological approach to combat pre-eclampsia is presented as a new direction to transfer from individualized risk to personalized prevention.
ISSN:1355-4786
1460-2369
DOI:10.1093/humupd/dmt003