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Umbilical Cord Blood Circulating Progenitor Cells and Endothelial Colony-Forming Cells Are Decreased in Preeclampsia

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Abstract

Preeclampsia (PE) is a pregnancy-specific disease characterized by the new onset of hypertension and proteinuria. Mothers with PE are known to develop endothelial dysfunction, but its effect on infants has been understudied, as newborns are often asymptomatic. Recent studies indicate that infants born from preeclamptic pregnancies develop endothelial dysfunction including higher blood pressure during childhood and an increased risk of stroke later in life. We hypothesize that PE reduces the number and function of fetal angiogenic progenitor cells and may contribute to this increased risk. We quantified 2 distinct types of angiogenic progenitors, pro-angiogenic circulating progenitor cells (CPCs) and endothelial colony-forming cells (ECFCs), from the umbilical cord blood of preeclamptic pregnancies and normotensive controls. Pro-angiogenic and non-angiogenic CPCs were enumerated via flow cytometry and ECFCs by cell culture. Additionally, we studied the growth, migration, and tube formation of ECFCs from PE and gestational age–matched normotensive control pregnancies. We found that PE resulted in decreased cord blood pro-angiogenic CPCs and ECFCs. Nonangiogenic CPCs were also decreased. Pre-eclamptic ECFCs demonstrated decreased growth and migration but formed tube-like structures in vitro similar to controls. Our results suggest that the preeclamptic environment alters the number and function of angiogenic progenitor cells and may increase the risk of later vascular disease.

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References

  1. Wu CS, Nohr EA, Bech BH, Vestergaard M, Catov JM, Olsen J. Health of children born to mothers who had preeclampsia: a population-based cohort study. Am J Obstet Gynecol. 2009; 201(3):269.e1–269.e10.

    Google Scholar 

  2. Ghulmiyyah L, Sibai B. Maternal mortality from preeclampsia/ eclampsia. Semin Perinatol. 2012;36(1):56–59.

    PubMed  Google Scholar 

  3. Kajantie E, Eriksson JG, Osmond C, Thornburg K, Barker DJ. Pre-eclampsia is associated with increased risk of stroke in the adult offspring: the Helsinki birth cohort study. Stroke. 2009;40(4):1176–1180.

    PubMed  Google Scholar 

  4. Seidman DS, Laor A, Gale R, Stevenson DK, Mashiach S, Danon YL. Pre-eclampsia and offspring’s blood pressure, cognitive ability and physical development at 17-years-of-age. Br J Obstet Gynaecol. 1991;98(10):1009–1014.

    CAS  PubMed  Google Scholar 

  5. Tenhola S, Rahiala E, Halonen P, Vanninen E, Voutilainen R. Maternal preeclampsia predicts elevated blood pressure in 12-year-old children: evaluation by ambulatory blood pressure monitoring. Pediatr Res. 2006;59(2):320–324.

    PubMed  Google Scholar 

  6. Vatten LJ, Romundstad PR, Holmen TL, Hsieh C, Trichopoulos D, Stuver SO. Intrauterine exposure to preeclampsia and adoles-cent blood pressure, body size, and age at menarche in female offspring. Obstet Gynecol. 2003;101(3):529–533.

    PubMed  Google Scholar 

  7. Giannotti G, Doerries C, Mocharla PS, et al. Impaired endothelial repair capacity of early endothelial progenitor cells in prehypertension: relation to endothelial dysfunction. Hypertension. 2010;55(6):1389–1397.

    CAS  PubMed  Google Scholar 

  8. Fadini GP, Miorin M, Facco M, et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol. 2005;45(9):1449–1457.

    CAS  PubMed  Google Scholar 

  9. Burnham EL, Taylor WR, Quyyumi AA, Rojas M, Brigham KL, Moss M. Increased circulating endothelial progenitor cells are associated with survival in acute lung injury. Am J Respir Crit Care Med. 2005;172(7):854–860.

    PubMed  Google Scholar 

  10. Rafat N, Hanusch C, Brinkkoetter PT, et al. Increased circulating endothelial progenitor cells in septic patients: correlation with survival. Crit Care Med. 2007;35(7):1677–1684.

    PubMed  Google Scholar 

  11. Vasa M, Fichtischerer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely cor-relate with risk factors for coronary artery disease. Circ Res. 2001; 89(1):E1–E7.

    CAS  PubMed  Google Scholar 

  12. Ghani U, Shuaib A, Salam A, et al. Endothelial progenitor cells during cerebrovascular disease. Stroke. 2005;36(1):151–153.

    PubMed  Google Scholar 

  13. Marti-Fàbregas J, Delgado-Mederos R, Crespo J, et al. Circulat-ing endothelial progenitor cells and the risk of vascular events after ischemic stroke. PLoS One. 2015;10(4):e0124895.

    PubMed  PubMed Central  Google Scholar 

  14. Boos CJ, Goon PK, Lip GY. Endothelial progenitor cells in the vascular pathophysiology of hypertension: arterial stiffness, age-ing and more. J Hum Hypertens. 2006;20(7):475–477.

    CAS  PubMed  Google Scholar 

  15. Monga R, Buck S, Sharma P, Thomas R, Chouthai NS. Effect of preeclampsia and intrauterine growth restriction on endothelial progenitor cells in human umbilical cord blood. J Matern Fetal Neonatal Med. 2012;25(11):2385–2389.

    PubMed  Google Scholar 

  16. Luppi P, Powers RW, Verma V, Edmunds L, Plymire D, Hubel CA. Maternal circulating CD34+VEGFR-2+ and CD133+ VEGFR-2+ progenitor cells increase during normal pregnancy but are reduced in women with preeclampsia. Reprod Sci. 2010;17(7):643–652.

    PubMed  Google Scholar 

  17. Liu X, Luo Q, Zheng Y, et al. Notchl impairs endothelial pro-genitor cell bioactivity in preeclampsia [published online May 18, 2016]. Reprod Sci. 2016.

    Google Scholar 

  18. Case J, Mead LE, Bessler WK, et al. Human CD34+ AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. Exp Hematol. 2007;35(7):1109–1118.

    CAS  PubMed  Google Scholar 

  19. Yoder MC, Mead LE, Prater D, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/ progenitor cell principals. Blood. 2007;109(5):1801–1809.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Ingram DA, Caplice NM, Yoder MC. Unresolved questions, changing definitions, and novel paradigms for defining endothe-lial progenitor cells. Blood. 2005;106(5):1525–1531.

    CAS  PubMed  Google Scholar 

  21. Duong HT, Erzurum SC, Asosingh K. Pro-angiogenic hemato-poietic progenitor cells and endothelial colony-forming cells in pathological angiogenesis of bronchial and pulmonary circulation. Angiogenesis. 2011;14(4):411–422.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Richardson MR, Yoder MC. Endothelial progenitor cells: quo vadis? J Mol Cell Cardiol. 2011;50(2):266–272.

    CAS  PubMed  Google Scholar 

  23. Baker CD, Balasubramaniam V, Mourani PM, et al. Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia. Eur Respir J. 2012;40(6):1516–1522.

    PubMed  PubMed Central  Google Scholar 

  24. Estes ML, Mund JA, Ingram DA, Case J. Identification of endothelial cells and progenitor cell subsets in human peripheral blood. Curr Protoc Cytom. 2010; Chapter 9:Unit 9.33.1–11.

    Google Scholar 

  25. Estes ML, Mund JA, Mead LE, et al. Application of polychro-matic flow cytometry to identify novel subsets of circulating cells with angiogenic potential. Cytometry A. 2010;77(9):831–839.

    PubMed  PubMed Central  Google Scholar 

  26. Acosta JC, Haas DM, Saha CK, Dimeglio LA, Ingram DA, Haneline LS. Gestational diabetes mellitus alters maternal and neonatal circulating endothelial progenitor cell subsets. Am J Obstet Gynecol. 2011;204(3):254.e8–254.e15.

    Google Scholar 

  27. Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood. 2004;104(9):2752–2760.

    CAS  PubMed  Google Scholar 

  28. Borghesi A, Massa M, Campanelli R, et al. Circulating endothelial progenitor cells in preterm infants with bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2009;180(6):540–546.

    PubMed  Google Scholar 

  29. Munoz-Hernandez R, Miranda ML, Stiefel P, et al. Decreased level of cord blood circulating endothelial colony-forming cells in preeclampsia. Hypertension. 2014;64(1):165–171.

    CAS  PubMed  Google Scholar 

  30. von Versen-Höynck F, Brodowski L, Dechend R, Myerski AC, Hubel CA. Vitamin D antagonizes negative effects of preeclamp-sia on fetal endothelial colony forming cell number and function. PLoS One. 2014;9(6):e98990.

    Google Scholar 

  31. Tita ATN, Andrews WW. Diagnosis and management of clinical chorioamnionitis. Clin Perinatol. 2010;37(2):339–354.

    PubMed  PubMed Central  Google Scholar 

  32. ACOG Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol. 2002;99(1):159–167.

    Google Scholar 

  33. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–381.

    PubMed  Google Scholar 

  34. Bikfalvi A, Cramer EM, Tenza D, Tobelem G. Phenotypic mod-ulations of human umbilical vein endothelial cells and human dermal fibroblasts using two angiogenic assays. Biol Cell. 1991;72(3):275–278.

    CAS  PubMed  Google Scholar 

  35. Ingram DA, Lien IZ, Mead LE, et al. In vitro hyperglycemia or a diabetic intrauterine environment reduces neonatal endothelial colony-forming cell numbers and function. Diabetes. 2008;57(3):724–731.

    CAS  PubMed  Google Scholar 

  36. Sipos PI, Bourque SL, Hubel CA, et al. Endothelial colony-forming cells derived from pregnancies complicated by intrauterine growth restriction are fewer and have reduced vasculogenic capacity. J Clin Endocrinol Metab. 2013;98(12):4953–4960.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Blue EK, DiGiuseppe R, Derr-Yellin E, et al. Gestational diabetes induces alterations in the function of neonatal endothelial colony-forming cells. Pediatr Res. 2014;75(2):266–272.

    CAS  PubMed  Google Scholar 

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Correspondence to Christopher D. Baker MD.

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Gumina, D.L., Black, C.P., Balasubramaniam, V. et al. Umbilical Cord Blood Circulating Progenitor Cells and Endothelial Colony-Forming Cells Are Decreased in Preeclampsia. Reprod. Sci. 24, 1088–1096 (2017). https://doi.org/10.1177/1933719116678692

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