pregnancy associated plasma protein A


Gene Symbol: pregnancy associated plasma protein A
Description: pappalysin 1
Alias: ASBABP2, DIPLA1, IGFBP-4ase, PAPA, PAPP-A, PAPPA1, pappalysin-1, IGF-dependent IGFBP-4 protease, aspecific BCL2 ARE-binding protein 2, differentially placenta 1 expressed protein, insulin-like growth factor-dependent IGF binding protein-4 protease, pregnancy-associated plasma protein A, pappalysin 1
Species: human

Top Publications

  1. D Elia P, Marzioni D, Castellucci M, Mocci C, Pala A. Homodimeric pregnancy-associated plasma protein-A in normal human placenta of first and third trimester of pregnancy: biochemical and morphological observations. Placenta. 2012;33:942-5 pubmed publisher
    ..In agreement with the above, dPAPP-A is released only by first trimester placental explants in culture. ..
  2. Sahraravand M, Järvelä I, Laitinen P, Tekay A, Ryynanen M. The secretion of PAPP-A, ADAM12, and PP13 correlates with the size of the placenta for the first month of pregnancy. Placenta. 2011;32:999-1003 pubmed publisher
    ..After 8 weeks of pregnancy, which is the time for luteoplacental shift, the correlation disappears, possibly reflecting the morphologic transformation in the placenta. ..
  3. Overgaard M, Haaning J, Boldt H, Olsen I, Laursen L, Christiansen M, et al. Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor. J Biol Chem. 2000;275:31128-33 pubmed
    ..Inhibition of PAPP-A by proMBP represents a novel inhibitory mechanism with the enzyme irreversibly bound to its inhibitor by disulfide bonds. ..
  4. Laursen L, Overgaard M, Weyer K, Boldt H, Ebbesen P, Christiansen M, et al. Cell surface targeting of pregnancy-associated plasma protein A proteolytic activity. Reversible adhesion is mediated by two neighboring short consensus repeats. J Biol Chem. 2002;277:47225-34 pubmed
    ..proMBP restores surface binding. We finally propose a model in which IGF bioactivity is regulated by reversible cell surface binding of PAPP-A, which in turn is regulated by proMBP. ..
  5. Kalousova M, Bartosova K, Zima T, Skibova J, Teplan V, Viklicky O. Pregnancy-associated plasma protein a and soluble receptor for advanced glycation end products after kidney transplantation. Kidney Blood Press Res. 2007;30:31-7 pubmed
    ..After successful TX, these substances decrease, and, on the contrary, early chronic vascular changes in the kidney TX are associated with elevation of their serum levels. ..
  6. Hajek P, Macek M, Hladikova M, Houbova B, Alan D, Durdil V, et al. Pregnancy-associated plasma protein A and proform eosinophilic major basic protein in the detection of different types of coronary artery disease. Physiol Res. 2008;57:23-32 pubmed
    ..75 mIU/l. Combination of PAPP-A/proMBP with cTnI increases their diagnostic efficacy within the early phase of ACS. Our results suggest that PAPP-A/proMBP complex is involved in processes preceding vulnerable plaque development in ACS. ..
  7. Consuegra Sanchez L, Fredericks S, Kaski J. Pregnancy-associated plasma protein-A (PAPP-A) and cardiovascular risk. Atherosclerosis. 2009;203:346-52 pubmed publisher
    ..The present article reviews currently available evidence supporting a role for PAPP-A as a marker of cardiovascular risk and discusses some of the pitfalls that may limit its use in clinical practice. ..
  8. Mikkelsen J, Gyrup C, Kristensen P, Overgaard M, Poulsen C, Laursen L, et al. Inhibition of the proteolytic activity of pregnancy-associated plasma protein-A by targeting substrate exosite binding. J Biol Chem. 2008;283:16772-80 pubmed publisher
  9. Oxvig C, Sand O, Kristensen T, Gleich G, Sottrup Jensen L. Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein. J Biol Chem. 1993;268:12243-6 pubmed
    ..In addition, it is shown that commercial polyclonal anti-PAPP-A is polyspecific, also reacting with MBP. ..

More Information


  1. Chen B, Leiferman K, Pittelkow M, Overgaard M, Oxvig C, Conover C. Localization and regulation of pregnancy-associated plasma protein a expression in healing human skin. J Clin Endocrinol Metab. 2003;88:4465-71 pubmed
    ..These data demonstrate localized and regulated expression of PAPP-A in human skin and suggest that PAPP-A may play an important role in an integrated IGF system in wound healing and tissue remodeling in vivo. ..
  2. Ortiz C, Chen B, Bale L, Overgaard M, Oxvig C, Conover C. Transforming growth factor-beta regulation of the insulin-like growth factor binding protein-4 protease system in cultured human osteoblasts. J Bone Miner Res. 2003;18:1066-72 pubmed
    ..These data support a model whereby local TGF-beta and IGF-II in the bone microenvironment coordinately amplify IGF-I bioavailability through controlled IGFBP-4 proteolysis, which may be a means to promote bone formation. ..
  3. Kalli K, Chen B, Bale L, Gernand E, Overgaard M, Oxvig C, et al. Pregnancy-associated plasma protein-A (PAPP-A) expression and insulin-like growth factor binding protein-4 protease activity in normal and malignant ovarian surface epithelial cells. Int J Cancer. 2004;110:633-40 pubmed
    ..The concurrent regulation of PAPP-A and its inhibitor, proMBP, suggests that IGFBP-4 proteolysis and local regulation of IGF availability may be altered in malignant ovarian epithelial cells. ..
  4. Kumar A, Mohan S, Newton J, Rehage M, Tran K, Baylink D, et al. Pregnancy-associated plasma protein-A regulates myoblast proliferation and differentiation through an insulin-like growth factor-dependent mechanism. J Biol Chem. 2005;280:37782-9 pubmed
  5. Glerup S, Kløverpris S, Laursen L, Dagnaes Hansen F, Thiel S, Conover C, et al. Cell surface detachment of pregnancy-associated plasma protein-A requires the formation of intermolecular proteinase-inhibitor disulfide bonds and glycosaminoglycan covalently bound to the inhibitor. J Biol Chem. 2007;282:1769-78 pubmed
    ..Because both PAPP-A and proMBP are expressed ubiquitously, this model may be applicable to many tissues in which insulin-like growth factor bioavailability is locally regulated. ..
  6. Iversen K, Dalsgaard M, Teisner A, Schoos M, Teisner B, Nielsen H, et al. Pregnancy-associated plasma protein-A, a marker for outcome in patients suspected for acute coronary syndrome. Clin Biochem. 2010;43:851-7 pubmed publisher
    ..4, p=0.01). In patients admitted with chest pain and both normal ECG and normal biomarkers PAPP-A seems to be valuable for predicting patients at high risk of death or non-fatal myocardial infarction. ..
  7. Lawrence J, Oxvig C, Overgaard M, Sottrup Jensen L, Gleich G, Hays L, et al. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc Natl Acad Sci U S A. 1999;96:3149-53 pubmed
    ..In conclusion, we have identified an IGF-dependent IGFBP protease and at the same time assigned a function to PAPP-A. This represents an unanticipated union of two areas of research that were not linked in any way before this report. ..
  8. Bonno M, Oxvig C, Kephart G, Wagner J, Kristensen T, Sottrup Jensen L, et al. Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta. Lab Invest. 1994;71:560-6 pubmed
    ..The presence of PAPP-A mRNA and PAPP-A subunit protein in placental X cells and syncytiotrophoblasts indicates that both X cells and syncytiotrophoblasts synthesize the PAPP-A subunit, whereas only X cells synthesize proMBP. ..
  9. Meloni P, D Angeli I, Piazze J, Cerekya A, Simari T, Pala A, et al. First trimester PAPP-A levels associated with early prediction of pregnancy induced hypertension. Hypertens Pregnancy. 2009;28:361-8 pubmed publisher
    ..The purpose of this study was to determine the predictive value of maternal PAPP-A levels in the identification of women at risk of PIH...
  10. Laursen L, Overgaard M, Søe R, Boldt H, Sottrup Jensen L, Giudice L, et al. Pregnancy-associated plasma protein-A (PAPP-A) cleaves insulin-like growth factor binding protein (IGFBP)-5 independent of IGF: implications for the mechanism of IGFBP-4 proteolysis by PAPP-A. FEBS Lett. 2001;504:36-40 pubmed
    ..We thus conclude that IGF enhances proteolysis by binding to IGFBP-4, not by interaction with PAPP-A, which could not previously be ruled out. ..
  11. Handschuh K, Guibourdenche J, Guesnon M, Laurendeau I, Evain Brion D, Fournier T. Modulation of PAPP-A expression by PPARgamma in human first trimester trophoblast. Placenta. 2006;27 Suppl A:S127-34 pubmed
    ..Since we have previously shown that PPARgamma agonist inhibits EVCT invasion in vitro, we suggest that PPARgamma-mediated inhibition of PAPP-A might decrease the amount of bioactive IGFII, a factor known to promote trophoblast invasion. ..
  12. Odibo A, Zhong Y, Longtine M, Tuuli M, Odibo L, Cahill A, et al. First-trimester serum analytes, biophysical tests and the association with pathological morphometry in the placenta of pregnancies with preeclampsia and fetal growth restriction. Placenta. 2011;32:333-8 pubmed publisher
    ..First-trimester PAPP-A levels are associated with abnormal placental morphometry at delivery in pregnancies with PE and IUGR. These findings may explain the association between adverse pregnancy outcomes and first-trimester PAPP-A. ..
  13. Overgaard M, Oxvig C, Christiansen M, Lawrence J, Conover C, Gleich G, et al. Messenger ribonucleic acid levels of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein: expression in human reproductive and nonreproductive tissues. Biol Reprod. 1999;61:1083-9 pubmed
    ..Both mRNA species were significantly more abundant in term placenta than in other tissues analyzed. All analyzed tissues, including endometrium, myometrium, colon, and kidney, contained both PAPP-A and proMBP mRNA. ..
  14. Kalousova M, Benakova H, Kubena A, Dusilova Sulkova S, Tesar V, Zima T. Pregnancy-associated plasma protein A as an independent mortality predictor in long-term hemodialysis patients. Kidney Blood Press Res. 2012;35:192-201 pubmed publisher
    ..PAPP-A was not related to cardiovascular mortality. Increased PAPP-A is a significant independent predictor of overall mortality and mortality due to infection but it was not related to cardiovascular mortality in this study. ..
  15. Bulut I, Coskun A, Ciftci A, Cetinkaya E, Altiay G, Caglar T, et al. Relationship between pregnancy-associated plasma protein-A and lung cancer. Am J Med Sci. 2009;337:241-4 pubmed publisher
    ..We found that the serum PAPP-A levels increased in patients with lung cancer and postulated that PAPP-A levels may be a prognostic factor in such cases. ..
  16. Lund J, Qin Q, Ilva T, Pettersson K, Voipio Pulkki L, Porela P, et al. Circulating pregnancy-associated plasma protein a predicts outcome in patients with acute coronary syndrome but no troponin I elevation. Circulation. 2003;108:1924-6 pubmed
  17. Guibourdenche J, Frendo J, Pidoux G, Bertin G, Luton D, Muller F, et al. Expression of pregnancy-associated plasma protein-A (PAPP-A) during human villous trophoblast differentiation in vitro. Placenta. 2003;24:532-9 pubmed
    ..In conclusion, PAPP-A production in vitro, is associated to the differentiation of villous cytotrophoblast cells into syncytiotrophoblast, independently of the age of gestation. ..
  18. Beaudeux J, Burc L, Imbert Bismut F, Giral P, Bernard M, Bruckert E, et al. Serum plasma pregnancy-associated protein A: a potential marker of echogenic carotid atherosclerotic plaques in asymptomatic hyperlipidemic subjects at high cardiovascular risk. Arterioscler Thromb Vasc Biol. 2003;23:e7-10 pubmed
  19. Kristensen T, Oxvig C, Sand O, Møller N, Sottrup Jensen L. Amino acid sequence of human pregnancy-associated plasma protein-A derived from cloned cDNA. Biochemistry. 1994;33:1592-8 pubmed
    ..Apart from these features, the PAPP-A sequence is not related to other known protein sequences. ..
  20. Tornehave D, Chemnitz J, Teisner B, Folkersen J, Westergaard J. Immunohistochemical demonstration of pregnancy-associated plasma protein A (PAPP-A) in the syncytiotrophoblast of the normal placenta at different gestational ages. Placenta. 1984;5:427-31 pubmed
    ..The results indicate that PAPP-A is probably synthesized in the syncytiotrophoblast. ..
  21. Catic A, Gurbeta L, Kurtovic Kozaric A, Mehmedbasic S, Badnjevic A. Application of Neural Networks for classification of Patau, Edwards, Down, Turner and Klinefelter Syndrome based on first trimester maternal serum screening data, ultrasonographic findings and patient demographics. BMC Med Genomics. 2018;11:19 pubmed publisher
    ..Developed Expert System proved to be simple, robust, and powerful in properly classifying prenatal aneuploidy syndromes. ..
  22. Hjortebjerg R, Lindberg S, Pedersen S, Mogelvang R, Jensen J, Oxvig C, et al. Insulin-Like Growth Factor Binding Protein 4 Fragments Provide Incremental Prognostic Information on Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction. J Am Heart Assoc. 2017;6: pubmed publisher
    ..IGFBP-4 fragments are associated with increased risk of all-cause mortality, cardiovascular mortality, and major adverse cardiac events in patients with ST-segment elevation myocardial infarction. ..
  23. Bulut I, Ozseker Z, Coskun A, Serteser M, Unsal I. Pregnancy-associated plasma protein-A (PAPP-A) levels in patients with severe allergic asthma are reduced by omalizumab. J Asthma. 2017;:1-6 pubmed publisher
    ..In the present study, we evaluated the effects of omalizumab on serum PAPP-A, IGFBP-4, and IGF-1 levels in subjects with severe allergic asthma...
  24. Peterson S, Simhan H. First-trimester pregnancy-associated plasma protein A and subsequent abnormalities of fetal growth. Am J Obstet Gynecol. 2008;198:e43-5 pubmed publisher
    ..The strong association between low PAPP-A and SGA warrants further investigation of its usefulness as a screening tool. ..
  25. Sá D, Festa C. Inflammasomes and dermatology. An Bras Dermatol. 2016;91:566-578 pubmed publisher
    ..Periodic Syndromes (CAPS), Familial Mediterranean Fever (FMF), Schnitzler Syndrome, Hyper-IgD Syndrome (HIDS), PAPA Syndrome, and Deficiency of IL-1 Receptor Antagonist (DIRA)...
  26. Garrido Gomez T, Ona K, Kapidzic M, Gormley M, Simon C, Genbacev O, et al. Severe pre-eclampsia is associated with alterations in cytotrophoblasts of the smooth chorion. Development. 2017;144:767-777 pubmed publisher
    ..g. placental proteins, markers of oxidative stress). We confirmed an sPE-related increase in production of PAPPA1, which releases IGF1 from its binding protein...
  27. Iversen K, Teisner A, Teisner B, Kliem A, Thanning P, Nielsen H, et al. Pregnancy associated plasma protein A, a potential marker for vulnerable plaque in patients with non-ST-segment elevation acute coronary syndrome. Clin Biochem. 2009;42:828-34 pubmed publisher
    To describe the presence and time-related pattern of circulating pregnancy associated plasma protein A (PAPP-A) levels in patients with non ST-segment elevation acute coronary syndrome (NSTE-ACS)...
  28. Li X, Liu Q, Zhou T, Zhao S, Zhou S. PAPP-A: a possible pathogenic link to the instability of atherosclerotic plaque. Med Hypotheses. 2008;70:597-9 pubmed
    ..b>Pregnancy associated plasma protein A (PAPP-A) is a member of the metzincin superfamily of metalloproteinases originally identified in ..
  29. Bøtkjær J, Borgbo T, Kløverpris S, Noer P, Oxvig C, Andersen C. Effect of pregnancy-associated plasma protein-A (PAPP-A) single-nucleotide polymorphisms on the level and activity of PAPP-A and the hormone profile in fluid from normal human small antral follicles. Fertil Steril. 2016;106:1778-1786.e8 pubmed publisher
    ..The 1224 SNP has previously been associated with recurrent pregnancy loss, so further evaluation of an underlying mechanism including aberrant control of insulin-like growth factor activity is warranted. ..
  30. O Gorman N, Wright D, Syngelaki A, Akolekar R, Wright A, Poon L, et al. Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation. Am J Obstet Gynecol. 2016;214:103.e1-103.e12 pubmed publisher
    ..Combination of maternal factors and biomarkers provides effective first-trimester screening for preterm-preeclampsia. ..
  31. Sonek J, Krantz D, Carmichael J, Downing C, Jessup K, Haidar Z, et al. First-trimester screening for early and late preeclampsia using maternal characteristics, biomarkers, and estimated placental volume. Am J Obstet Gynecol. 2018;218:126.e1-126.e13 pubmed publisher
    ..In this study the utility of estimated placental volume and mean arterial pressure was limited but larger studies are needed to ultimately determine the effectiveness of these markers. ..
  32. Aggarwal S, Sunderland N, Thornton C, Xu B, Hennessy A, Makris A. A longitudinal analysis of angiotensin II type 1 receptor antibody and angiogenic markers in pregnancy. Am J Obstet Gynecol. 2017;216:170.e1-170.e8 pubmed publisher
    ..Angiotensin II type 1 receptor antibody (12 weeks) was positively correlated with serum pregnancy associated plasma protein A (P = .008) and human chorionic gonadotrophin (P = .04)...
  33. Oxvig C, Haaning J, Kristensen L, Wagner J, Rubin I, Stigbrand T, et al. Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma. J Biol Chem. 1995;270:13645-51 pubmed
    ..These results suggest that specific interactions between the complexed proteins occur in pregnancy, and the possibility is raised that their interactions are important in the pathophysiology of pregnancies associated with hypertension. ..
  34. Duckworth S, Griffin M, Seed P, North R, Myers J, Mackillop L, et al. Diagnostic Biomarkers in Women With Suspected Preeclampsia in a Prospective Multicenter Study. Obstet Gynecol. 2016;128:245-52 pubmed publisher
    ..88; P=.40). This study supports the growing body of evidence that a single angiogenesis-related biomarker (PlGF, sFlt-1, or endoglin) alone represents a useful diagnostic test for women presenting with suspected preterm preeclampsia. ..
  35. Silahtaroglu A, Tumer Z, Kristensen T, Sottrup Jensen L, Tommerup N. Assignment of the human gene for pregnancy-associated plasma protein A (PAPPA) to 9q33.1 by fluorescence in situ hybridization to mitotic and meiotic chromosomes. Cytogenet Cell Genet. 1993;62:214-6 pubmed
    ..We have assigned the locus for PAPPA to chromosome region 9q33.1 on mitotic and meiotic chromosomes by fluorescence in situ hybridization, using a 3.7-kb partial PAPPA cDNA probe. ..
  36. Lodh M, Goswami B, Parida A, Patra S, Saxena A. Assessment of serum leptin, pregnancy-associated plasma protein A and CRP levels as indicators of plaque vulnerability in patients with acute coronary syndrome. Cardiovasc J Afr. 2012;23:330-5 pubmed publisher
    ..Our findings necessitate population-based follow-up studies to establish the superiority of either of the two biomarkers in the field of preventive cardiology. ..
  37. Omenetti A, Carta S, Caorsi R, Finetti M, Marotto D, Lattanzi B, et al. Disease activity accounts for long-term efficacy of IL-1 blockers in pyogenic sterile arthritis pyoderma gangrenosum and severe acne syndrome. Rheumatology (Oxford). 2016;55:1325-35 pubmed publisher
    To provide a rationale for anti-IL-1 treatment in pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) by defining whether IL-1? secretion is enhanced; requires NLRP3; and correlates with proline-serine-threonine phosphatase-..
  38. Huet N, Rodiere M, Badet M, Michoud M, Brichon P, Ferretti G, et al. Covered Stent and Coils Embolization of a Pulmonary Artery Pseudoaneurysm After Gunshot Wound. Cardiovasc Intervent Radiol. 2016;39:778-81 pubmed publisher
    ..first case of endovascular covered stent implantation for the treatment of a large pulmonary artery pseudoaneurysm (PAPA) following a right thoracic gunshot wound...
  39. Agopian A, Mitchell L, Glessner J, Bhalla A, Sewda A, Hakonarson H, et al. Genome-wide association study of maternal and inherited loci for conotruncal heart defects. PLoS ONE. 2014;9:e96057 pubmed publisher
    ..2 × 10(-6)). These observations suggest novel candidate loci for CTDs, including loci that appear to be associated with the risk of CTDs via the maternal genotype, but further studies are needed to confirm these associations. ..
  40. Wu X, Liu X, Dong J, Wang L, Yang Y, Nie S, et al. Pregnancy-associated plasma protein-A as a marker of culprit lesion instability in unstable angina patients: an intravascular ultrasound study. Cardiology. 2013;126:244-51 pubmed publisher
    ..Higher PAPP-A levels were associated with coronary plaque instability in vivo and unstable symptoms in patients with coronary artery disease. ..
  41. Chougrani I, Muller F, MARCELIN L, Tsatsaris V, Abric J, Luton D, et al. Combined first-trimester Down syndrome screening in HIV-infected women. Eur J Obstet Gynecol Reprod Biol. 2016;203:274-8 pubmed publisher
    ..First-trimester DS combined screening biomarker levels and calculated risk do not seem to be significantly altered by HIV infection or antiretroviral treatment. This screening strategy appears to be suitable for HIV-infected women. ..
  42. Stoykova V, Vagarova R, Markov D, Kremensky I, Ivanov S. [Low PAPP-A levels between 11 and 13(+6) weeks of gestation and the risk of preeclampsia]. Akush Ginekol (Sofiia). 2010;49:19-25 pubmed
    ..When low PAPP-A levels are added to the maternal age and especially results of Doppler evaluation of the uterine arteries significant prognostic value improvement was observed. ..
  43. Wang F, He Q, Su K, Wei T, Xu S, Gu L. Structural and biochemical characterization of the catalytic domains of GdpP reveals a unified hydrolysis mechanism for the DHH/DHHA1 phosphodiesterase. Biochem J. 2018;475:191-205 pubmed publisher
    ..c-di-AMP) could be subdivided into two subfamilies based on the final product [5'-phosphadenylyl-adenosine (5'-pApA) or AMP]...
  44. Hanna C, Bretherick K, Liu C, Stephenson M, Robinson W. Genetic variation within the hypothalamus-pituitary-ovarian axis in women with recurrent miscarriage. Hum Reprod. 2010;25:2664-71 pubmed publisher
  45. Ziviello F, Conte S, Cimmino G, Sasso F, Trimarco B, Cirillo P. Pregnancy-Associated Plasma Protein-A and its Role in Cardiovascular Disease. Biology, Experimental/Clinical Evidences and Potential Therapeutic Approaches. Curr Vasc Pharmacol. 2017;15:197-206 pubmed publisher
    ..Finally, we discuss possible therapeutic approaches to antagonize its potential detrimental CV effects...
  46. Donaubauer E, Hunzicker Dunn M. Extracellular Signal-regulated Kinase (ERK)-dependent Phosphorylation of Y-Box-binding Protein 1 (YB-1) Enhances Gene Expression in Granulosa Cells in Response to Follicle-stimulating Hormone (FSH). J Biol Chem. 2016;291:12145-60 pubmed publisher
    ..Collectively, our results reveal that phosphorylation of YB-1 on Ser(102) via the ERK/RSK-2 signaling pathway is necessary for FSH-mediated expression of target genes required for maturation of follicles to a preovulatory phenotype. ..
  47. O Gorman N, Nicolaides K, Poon L. The use of ultrasound and other markers for early detection of preeclampsia. Womens Health (Lond). 2016;12:199-207 pubmed publisher
  48. Lopez Abad M, Iglesias Platas I, Monk D. Epigenetic Characterization of CDKN1C in Placenta Samples from Non-syndromic Intrauterine Growth Restriction. Front Genet. 2016;7:62 pubmed publisher
    ..All placenta biopsies heterozygous for the PAPA repeat sequence in exon 2 showed appropriate monoallelic expression and no mutations in the PCNA domain were ..
  49. He Q, Wang F, Liu S, Zhu D, Cong H, Gao F, et al. Structural and Biochemical Insight into the Mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP Phosphodiesterase. J Biol Chem. 2016;291:3668-81 pubmed publisher
    ..Here, we report the crystal structure of Rv2837c (2.0 Å), and its complex with hydrolysis intermediate 5'-pApA (2.35 Å). Our structures indicate that both DHH and DHHA1 domains are essential for c-di-AMP degradation...
  50. Liu Y, Ye X, Zhang N, Zhang B, Guo C, Huang W, et al. Diagnostic value of ultrasonographic combining biochemical markers for Down syndrome screening in first trimester: a meta-analysis. Prenat Diagn. 2015;35:879-87 pubmed publisher
  51. Mihelčić M, Simic G, Babić Leko M, Lavrac N, Dzeroski S, Smuc T. Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer's disease patients. PLoS ONE. 2017;12:e0187364 pubmed publisher
    ..Therefore, further studies should investigate the role of PAPP-A in the development of AD more thoroughly...
  52. Zorin N, Zhabin S, Semenkov N. Interaction of human pregnancy-associated plasma protein-A with serine proteinases. Clin Chim Acta. 1995;239:47-55 pubmed
    ..The mechanism of proteinase inhibition was likely to be entrapment, as described for alpha 2-macroglobulin. ..
  53. Karsli M, Baser E, Seckin K, Yeral M, Toğrul C, Ugur M. The impact of inherited thrombophilia on first trimester combined aneuploidy screening test parameters. J Matern Fetal Neonatal Med. 2014;27:346-9 pubmed publisher
    ..001). Our study suggested that PAPP-A, free b-HCG and NT MoM levels display alterations in women with inherited thrombophilia. Future trials are needed to assess the need for readjustment of risk in these patients. ..
  54. Yu M, Wang J, Liu S, Wang X, Yan Q. Novel function of pregnancy-associated plasma protein A: promotes endometrium receptivity by up-regulating N-fucosylation. Sci Rep. 2017;7:5315 pubmed publisher
    ..In summary, this study suggests that PAPPA is essential to maintain a receptive endometrium by up-regulating N-fucosylation, which is a potential useful biomarker to evaluate the receptive functions of the endometrium. ..
  55. Zakiyanov O, Kalousova M, Kratochvilová M, Kříha V, Zima T, Tesar V. Determinants of circulating matrix metalloproteinase-2 and pregnancy-associated plasma protein-A in patients with chronic kidney disease. Clin Lab. 2012;58:471-80 pubmed
    ..Our results suggest the possibility that circulating MMP-2 and PAPP-A be used as indicators for renal damage in CKD patients on conservative treatment. ..
  56. Vişan V, Anghelache Lupascu I, Sălăvăscu T, Rugină V, Socolov R, Socolov D, et al. INTRAUTERINE GROWTH RESTRICTION--PREDICTIVE SERUM MARKERS. Rev Med Chir Soc Med Nat Iasi. 2016;120:173-7 pubmed
  57. Jia D, Heersche J. Pregnancy-associated plasma protein-A proteolytic activity in rat vertebral cell cultures: stimulation by dexamethasone--a potential mechanism for glucocorticoid regulation of osteoprogenitor proliferation and differentiation. J Cell Physiol. 2005;204:848-58 pubmed
    ..Our findings underscore a novel mechanism whereby GCs increase IGF responses in rat bone cells via PAPP-A-induced IGFBP-4 proteolysis. ..
  58. Oxvig C. The role of PAPP-A in the IGF system: location, location, location. J Cell Commun Signal. 2015;9:177-87 pubmed publisher
    ..By taking advantage of the intricate interaction between PAPP-A and IGFBP-4, highly specific and selective inhibition of PAPP-A is possible. ..
  59. Dunne C, Cho K, Shan A, Hutcheon J, Durland U, Seethram K, et al. Peak Serum Estradiol Level During Controlled Ovarian Stimulation Is not Associated with Lower Levels of Pregnancy-Associated Plasma Protein-A or Small for Gestational Age Infants: A Cohort Study. J Obstet Gynaecol Can. 2017;39:870-879 pubmed publisher
    ..30). Our results do not support the theory that high E2 at fresh embryo transfer impedes placentation. We found no association between peak E2 and low PAPP-A levels or adverse pregnancy outcomes. ..
  60. Keikkala E, Koskinen S, Vuorela P, Laivuori H, Romppanen J, Heinonen S, et al. First trimester serum placental growth factor and hyperglycosylated human chorionic gonadotropin are associated with pre-eclampsia: a case control study. BMC Pregnancy Childbirth. 2016;16:378 pubmed
    ..First trimester maternal serum %hCG-h tended to improve prediction of preterm and early-onset pre-eclampsia when combined with PlGF, PAPP-A and maternal risk factors. ..
  61. Ball S, Wright D, Sodre D, Lachmann R, Nicolaides K. Temporal effect of Afro-Caribbean race on serum pregnancy-associated plasma protein-a at 9-13 weeks' gestation in screening for aneuploidies. Fetal Diagn Ther. 2012;31:162-9 pubmed publisher
    ..9% (95% CI 2.1-7.8). Serum-free ?-hCG and PAPP-A concentrations at 9(+0)-13(+6) weeks' gestation are affected by several pregnancy characteristics and the effect of Afro-Caribbean race on PAPP-A increases with gestational age. ..
  62. Syngelaki A, Kotecha R, Pastides A, Wright A, Nicolaides K. First-trimester biochemical markers of placentation in screening for gestational diabetes mellitus. Metabolism. 2015;64:1485-9 pubmed publisher
    ..053, 95% CI 1.023-1.083 MoM) (p=0.004). The performance of screening for GDM by maternal factors was not improved by the addition of PAPP-A and/or PLGF. First trimester maternal serum PAPP-A and PLGF are not useful in screening for GDM. ..
  63. Olanrewaju H, Qin W, Feoktistov I, Scemama J, Mustafa S. Adenosine A(2A) and A(2B) receptors in cultured human and porcine coronary artery endothelial cells. Am J Physiol Heart Circ Physiol. 2000;279:H650-6 pubmed
    ..yl¿eth yl]phenyl]ethylamino-5'- ethylcarboxamidoadenosine ((125)I-PAPA-APEC) (PAPA-APEC) was used to demonstrate the specific binding in PCAEC membranes...
  64. Iversen K, Teisner A, Teisner B, Kliem A, Bay M, Kirk V, et al. Pregnancy-associated plasma protein A in non-cardiac conditions. Clin Biochem. 2008;41:548-53 pubmed publisher
    ..PAPP-A is low in patients without known coronary heart disease. PAPP-A levels seem to be a potentially highly specific marker for heart disease. ..
  65. Conover C, Bale L, Nair K. Comparative gene expression and phenotype analyses of skeletal muscle from aged wild-type and PAPP-A-deficient mice. Exp Gerontol. 2016;80:36-42 pubmed publisher
    ..Moreover, 18-month-old PAPP-A KO mice exhibited significantly enhanced endurance running on a treadmill. Thus, PAPP-A deficiency in mice is associated with indices of healthy skeletal muscle function with age. ..
  66. Talay F, Tosun M, Yasar Z, Kar Kurt O, Karğı A, Ozturk S, et al. Evaluation of Pregnancy-Associated Plasma Protein-A Levels in Patients with Chronic Obstructive Pulmonary Disease and Associations with Disease Severity. Inflammation. 2016;39:1130-3 pubmed publisher
    ..58?±?22.98) and stage 4 (27.36?±?21.46) (p?=?0.049). Increased PAPP-A levels may be a useful marker in management of COPD that seeks to prevent the development of comorbidities such as adverse cardiovascular diseases. ..
  67. Suman P, Shembekar N, Gupta S. Leukemia inhibitory factor increases the invasiveness of trophoblastic cells through integrated increase in the expression of adhesion molecules and pappalysin 1 with a concomitant decrease in the expression of tissue inhibitor of matrix metalloprote. Fertil Steril. 2013;99:533-42 pubmed publisher
    ..Among 237 differentially expressed genes after LIF treatment, expression of pappalysin 1, SERPINB3, podoplanin, integrin ?3, ID1, ICAM1, and so on went up, while tissue inhibitor of matrix ..
  68. de Villiers C, Hedley P, Placing S, Wøjdemann K, Shalmi A, Carlsen A, et al. Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia. Clin Chem Lab Med. 2017;56:65-74 pubmed publisher
    ..However, the discriminatory ability of PP13 in first trimester has not been completely clarified...
  69. Huang T, Dennis A, Meschino W, Rashid S, Mak Tam E, Cuckle H. First trimester screening for Down syndrome using nuchal translucency, maternal serum pregnancy-associated plasma protein A, free-β human chorionic gonadotrophin, placental growth factor, and α-fetoprotein. Prenat Diagn. 2015;35:709-16 pubmed publisher
    ..3%, from 19.3% to 11.0%. At 3% FPR, DR using first trimester quad test was 76.4%. The performance of FTS can be enhanced by adding PlGF and AFP. Even without nuchal translucency, the test would perform well. ..
  70. Jauniaux E, Gulbis B, Jamil A, Jurkovic D. Evaluation of the role of maternal serum high-sensitivity C-reactive protein in predicting early pregnancy failure. Reprod Biomed Online. 2015;30:268-74 pubmed publisher
  71. Kalousova M, Jachymova M, Muravská A, Kubena A, Dusilova Sulkova S, Tesar V, et al. Cys327Cys polymorphism of the PAPP-A gene (pregnancy associated plasma protein A) is related to mortality of long term hemodialysis patients. Clin Biochem. 2014;47:578-83 pubmed publisher
    ..Although it does not influence the concentration of PAPP-A it still could affect the correct function of this enzyme which has to be clarified in further studies. ..
  72. Kirkegaard I, Uldbjerg N, Tabor A, Henriksen T. Longer time-to-pregnancy in spontaneously conceived pregnancies is associated with lower PAPP-A and free ?-hCG in first trimester screening for Down syndrome. Prenat Diagn. 2014;34:235-40 pubmed publisher
    ..4, 95% confidence interval; 0.8-2.4). Time-to-pregnancy ?24?months in spontaneously conceived pregnancies is associated with decreased levels of PAPP-A and free ?-hCG. ..
  73. Horton J, Maass D, White J, Sanders B. Nitric oxide modulation of TNF-alpha-induced cardiac contractile dysfunction is concentration dependent. Am J Physiol Heart Circ Physiol. 2000;278:H1955-65 pubmed
    ..S-nitroso-N-acetyl-penicillamine (SNAP) or (Z)-1- [N-(3-ammonio-propyl)-N-(n-propyl)amino]diazen-1-ium- 1,2diolate (PAPA/NO) on TNF-alpha-related changes in cardiac contractile function (Langendorff), cellular injury, and intracellular ..
  74. Chen B, Overgaard M, Bale L, Resch Z, Christiansen M, Oxvig C, et al. Molecular regulation of the IGF-binding protein-4 protease system in human fibroblasts: identification of a novel inducible inhibitor. Endocrinology. 2002;143:1199-205 pubmed
    ..These findings expand our understanding of the IGFBP-4 protease system and suggest an additional level of local cell growth control. ..
  75. Dembic M, Hedley P, Torp Pedersen C, Køber L, Christiansen M. Pregnancy-associated plasma protein-A (PAPP-A) and the proform of the eosinophil major basic protein (ProMBP) are associated with increased risk of death in heart failure patients. Scand J Clin Lab Invest. 2017;77:352-357 pubmed publisher
    ..In conclusion, high levels of PAPP-A and proMBP are associated with increased risk of death from all causes in HF and are potential prognostic markers of adverse outcomes in HF patients. ..
  76. McIntyre J, Hsi B, Faulk W, Klopper A, Thomson R. Immunological studies of the human placenta: functional and morphological analysis of pregnancy-associated plasma protein A (PAPP-A). Immunology. 1981;44:577-83 pubmed
    ..Neither antiserum nor antigen exerts a cytotoxic effect on peripheral blood lymphocytes, and neither affected blastogenic responses of lymphocytes to mitogens or in mixed lymphocyte culture reactions. ..
  77. Sivanandam A, Mohan S, Kita H, Kapur S, Chen S, Linkhart T, et al. Studies on regulation of IGF (insulin-like growth factor)-binding protein (IGFBP) 4 proteolysis by pregnancy-associated plasma protein-A (PAPP-A) in cells treated with phorbol ester. Biochem J. 2004;379:57-64 pubmed
    ..These data suggest that a novel mechanism, namely conversion of PAPP-A470 to the less-active PAPP-A400, could account for the TPA-induced suppression of PAPP-A activity. ..
  78. Bestwick J, Huttly W, Wald N. First trimester Down's syndrome screening marker values and cigarette smoking: new data and a meta-analysis on free beta human chorionic gonadotophin, pregnancy-associated plasma protein-A and nuchal translucency. J Med Screen. 2008;15:204-6 pubmed publisher
  79. Laursen L, Overgaard M, Nielsen C, Boldt H, Hopmann K, Conover C, et al. Substrate specificity of the metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) assessed by mutagenesis and analysis of synthetic peptides: substrate residues distant from the scissile bond are critical for proteolysis. Biochem J. 2002;367:31-40 pubmed
  80. Conover C, Mason M, Bale L, Harrington S, Nyegaard M, Oxvig C, et al. Transgenic overexpression of pregnancy-associated plasma protein-A in murine arterial smooth muscle accelerates atherosclerotic lesion development. Am J Physiol Heart Circ Physiol. 2010;299:H284-91 pubmed publisher
    ..These data provide further evidence for the importance of PAPP-A in the cardiovascular system and suggest PAPP-A as a potential therapeutic target in the control of atherosclerosis. ..
  81. Kalousova M, Zima T, Krane V, März W, Wanner C, Tesar V, et al. Pregnancy-associated plasma protein A associates with cardiovascular events in diabetic hemodialysis patients. Atherosclerosis. 2014;236:263-9 pubmed publisher
    ..PAPP-A is associated with sudden death, stroke and infectious complications in diabetic dialysis patients. PAPP-A may be useful for risk assessment and monitoring in populations at high risk of cardiovascular events. ..
  82. Heinig J, Steinhard J, Schmitz R, Nofer J, Kiesel L, Klockenbusch W. Influence of maternal systemic lupus erythematosus on first-trimester combined screening for chromosomal abnormalities. Prenat Diagn. 2007;27:600-2 pubmed
    ..But, because of the multimodal procedure of risk calculation there is no significant difference in the screen-positive rate after the combined first-trimester screening for trisomy 21. ..
  83. Takabatake Y, Oxvig C, Nagi C, Adelson K, Jaffer S, Schmidt H, et al. Lactation opposes pappalysin-1-driven pregnancy-associated breast cancer. EMBO Mol Med. 2016;8:388-406 pubmed publisher
    ..Our results offer the first mechanism that explains the link between breast cancer, pregnancy, and breastfeeding. ..
  84. You L, Li L, Zhang F, Xu Q, Ren J. A pilot study of the clinical relevance of the relationship between the serum level of pregnancy-associated plasma protein A and the degree of acute coronary syndrome. J Int Med Res. 2010;38:625-32 pubmed
    ..It would seem, therefore, that PAPP-A is associated with inflammation and might be used to detect plaque instability and rupture before an increase in cardiac troponin T is detectable. ..
  85. O Gorman N, Wright D, Rolnik D, Nicolaides K, Poon L. Study protocol for the randomised controlled trial: combined multimarker screening and randomised patient treatment with ASpirin for evidence-based PREeclampsia prevention (ASPRE). BMJ Open. 2016;6:e011801 pubmed publisher
    ..As of April 2016, 26 670 women have been screened and 1760 recruited to the RCT. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. ISRCTN13633058. ..
  86. Hasegawa J, Farina A, Simonazzi G, Bisulli M, Puccetti C, Pilu G, et al. Umbilical cord insertion into the lower segment of the uterus at 11 to 13 weeks' gestation is associated with maternal serum PAPP-A. Prenat Diagn. 2011;31:434-8 pubmed publisher
    ..16 ± 0.55; p = 0.009), whereas the other ultrasonographic measurements and maternal demographics were not different between the two groups. CI on the lower segment of the uterus is associated with low maternal serum PAPP-A MoM levels. ..
  87. Coskun A, Duran S, Apaydin S, Bulut I, Sariyar M. Pregnancy-associated plasma protein-A: evaluation of a new biomarker in renal transplant patients. Transplant Proc. 2007;39:3072-6 pubmed
    ..05). We concluded that PAPP-A level was elevated in renal transplant patients and that high levels of PAPP-A might be a prognostic marker owing to their close association with high serum levels of urea, creatinine, uric acid, and CRP. ..