Current Hypertension Reports

, 21:69 | Cite as

A Review of Angiogenic Imbalance in HIV-Infected Hypertensive Disorders of Pregnancy

  • Sayuri PadayacheeEmail author
  • Jagidesa Moodley
  • Thajasvarie Naicker
Preeclampsia (V Garovic, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Preeclampsia


Purpose of Review

This review provides a comprehensive insight into the angiogenic profile of hypertensive and normotensive pregnancies compromised by HIV infection. Furthermore, we evaluate the economic implementation of the sFlt-1/PlGF ratio and review the reports on therapeutic apheresis in limiting sFlt-1 production.

Recent Findings

In preeclampsia, an increased expression of sFlt-1 triggers angiogenic imbalance. Women of African ancestry have high levels of angiogenic factors than other racial groups. The sFlt-1/PlGF ratio shows promise in the early assessment of preeclampsia, while sFlt-1 apheresis restores angiogenic imbalance. Studies suggest antiretroviral therapy does not impact the angiogenic shift in preeclampsia development.


The angiogenic profile in pregnant women of different races influences preeclampsia development. Despite the opposing immune response in HIV infection and preeclampsia, the HIV tat protein strongly mimics vascular endothelial growth factor (VEGF); hence, it is plausible to assume that HIV infection may ameliorate the angiogenic imbalance in preeclampsia.


Angiogenesis Preeclampsia Soluble fms-like tyrosine kinase 1 Vascular endothelial growth factor Placental growth factor HIV 


Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Maynard SE, Karumanchi SA. Angiogenic factors and preeclampsia. Semin Nephrol. 2011;31(1):33–46.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Zygmunt M, Herr F, Münstedt K, Lang U, Liang OD. Angiogenesis and vasculogenesis in pregnancy. Eur J Obstet Gynecol Reprod Biol. 2003;110:S10–8.PubMedGoogle Scholar
  3. 3.
    Palei AC, et al. athophysiology of hypertension in preeclampsia: a lesson in integrative physiology. Acta Physiol (Oxford, England). 2013;208(3):224–33.Google Scholar
  4. 4.
    Muto H, Yamamoto R, Ishii K, Kakubari R, Takaoka S, Mabuchi A, et al. Risk assessment of hypertensive disorders in pregnancy with maternal characteristics in early gestation: a single-center cohort study. Taiwan J Obstet Gynecol. 2016;55(3):341–5.PubMedGoogle Scholar
  5. 5.
    •• Brown MA, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2018; New guidelines and classification for the diagnosis of hypertension in pregnancy by the ISSHP. Google Scholar
  6. 6.
    Browne JL, Schrier VJMM, Grobbee DE, Peters SAE, Klipstein-Grobusch K. HIV, antiretroviral therapy, and hypertensive disorders in pregnancy: a systematic review and meta-analysis. J Acquir Immune Defic Syndr. 2015;70(1):91–8.PubMedGoogle Scholar
  7. 7.
    Umesawa M, Kobashi G. Epidemiology of hypertensive disorders in pregnancy: prevalence, risk factors, predictors and prognosis. Hypertens Res. 2017;40(3):213–20.PubMedGoogle Scholar
  8. 8.
    •• Sebitloane HM, Moodley J, Sartorius B. Associations between HIV, highly active anti-retroviral therapy, and hypertensive disorders of pregnancy among maternal deaths in South Africa 2011–2013. Int J Gynaecol Obstet. 2017;136(2):195–9. A retrospective secondary analysis of maternal-deaths data from the 2011–2013 South African Saving Mothers Report to investigate the association between HAART and HDP among maternal deaths. PubMedGoogle Scholar
  9. 9.
    Statistics, Mid-Year Population Estimates 2018. Statistics South Africa. 2018.Google Scholar
  10. 10.
    UNAIDS, Ending AIDS: Progress towards the 90–90-90 targets. 2018.Google Scholar
  11. 11.
    • Cerdeira AS, et al. Angiogenic factors: potential to change clinical practice in pre-eclampsia? BJOG. 2018;125(11):1389–95. A review of the recent evidence of the potential of angiogenic factors as biomarkers and therapeutic agents for PE. PubMedGoogle Scholar
  12. 12.
    Wang A, Rana S, Karumanchi SA. Preeclampsia: the role of angiogenic factors in its pathogenesis. Physiology (Bethesda). 2009;24:147–58.Google Scholar
  13. 13.
    Gathiram P, Moodley J. Pre-eclampsia: its pathogenesis and pathophysiolgy. Cardiovasc J Africa. 2016;27(2):71–8.Google Scholar
  14. 14.
    von Dadelszen P, Magee LA, Roberts JM. Subclassification of preeclampsia. Hypertens Pregnancy. 2003;22(2):143–8.Google Scholar
  15. 15.
    Raymond D, Peterson E. A critical review of early-onset and late-onset preeclampsia. Obstet Gynecol Surv. 2011;66(8):497–506.PubMedGoogle Scholar
  16. 16.
    Felmeden DC, et al. Endothelial damage and angiogenesis in hypertensive patients: relationship to cardiovascular risk factors and risk factor management. Am J Hypertens. 2003;16(1):11–20.PubMedGoogle Scholar
  17. 17.
    Feihl F, et al. Hypertension: a disease of the microcirculation? Hypertension. 2006;48(6):1012–7.PubMedGoogle Scholar
  18. 18.
    Cheng C, Diamond JJ, Falkner B. Functional capillary rarefaction in mild blood pressure elevation. Clinical and translational science. 2008;1(1):75–9.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111(5):649–58.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672–83.PubMedGoogle Scholar
  21. 21.
    Rana S, Powe CE, Salahuddin S, Verlohren S, Perschel FH, Levine RJ, et al. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation. 2012;125(7):911–9.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Jakovljevic A, Bogavac M, Lozanov-Crvenkovic Z, Milosević-Tosic M, Nikolic A, Mitic G. Early pregnancy angiogenic proteins levels and pregnancy related hypertensive disorders. J Matern Fetal Neonatal Med. 2017;30(5):534–9.PubMedGoogle Scholar
  23. 23.
    Belgore FM, Blann AD, Li-Saw-Hee FL, Beevers DG, Lip GYH. Plasma levels of vascular endothelial growth factor and its soluble receptor (SFlt-1) in essential hypertension. Am J Cardiol. 2001;87(6):805–7 a9.PubMedGoogle Scholar
  24. 24.
    Helmo FR, Lopes AMM, Carneiro ACDM, Campos CG, Silva PB, dos Reis Monteiro MLG, et al. Angiogenic and antiangiogenic factors in preeclampsia. Pathol Res Pract. 2018;214(1):7–14.PubMedGoogle Scholar
  25. 25.
    • Shange GP, Moodley J, Naicker T. Effect of vascular endothelial growth factors A, C, and D in HIV-associated pre-eclampsia. Hypertens Pregnancy. 2017;36(2):196–203. A novel South African study investigating the VEGF family in an HIV-infected preeclamptic population. PubMedGoogle Scholar
  26. 26.
    •• Ngene NC, Moodley J. Role of angiogenic factors in the pathogenesis and management of pre-eclampsia. Int J Gynaecol Obstet. 2018;141(1):5–13. A review of the current literature on the pathogenesis of PE, with particular focus on the role of angiogenic factors. The clinical management of PE is also reviewed. PubMedGoogle Scholar
  27. 27.
    Shibuya M. Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases. J Biochem. 2013;153(1):13–9.PubMedGoogle Scholar
  28. 28.
    Robinson ES, Khankin EV, Choueiri TK, Dhawan MS, Rogers MJ, Karumanchi SA, et al. Suppression of the nitric oxide pathway in metastatic renal cell carcinoma patients receiving vascular endothelial growth factor-signaling inhibitors. Hypertension. 2010;56(6):1131–6.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Saleh L, Danser JA, van den Meiracker AH. Role of endothelin in preeclampsia and hypertension following antiangiogenesis treatment. Curr Opin Nephrol Hypertens. 2016;25(2):94–9.PubMedGoogle Scholar
  30. 30.
    • Karumanchi SA. Angiogenic factors in preeclampsia: from diagnosis to therapy. Hypertension. 2016;67(6):1072–9. A review discussing the pathogenesis of angiogenic factors in the maternal syndrome of PE and the role of these factors in the diagnosis and treatment of PE. PubMedGoogle Scholar
  31. 31.
    Eremina V, Sood M, Haigh J, Nagy A, Lajoie G, Ferrara N, et al. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest. 2003;111(5):707–16.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Nikuei P, et al. Expression of placental growth factor mRNA in preeclampsia. Int J Reprod Biomed (Yazd, Iran). 2017;15(3):169–74.Google Scholar
  33. 33.
    Andraweera PH, Dekker GA, Laurence JA, Roberts CT. Placental expression of VEGF family mRNA in adverse pregnancy outcomes. Placenta. 2012;33(6):467–72.PubMedGoogle Scholar
  34. 34.
    Furuya M, et al. Disrupted balance of angiogenic and antiangiogenic signalings in preeclampsia. J Pregnancy. 2011;2011:123717.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Mizuuchi M, Cindrova-Davies T, Olovsson M, Charnock-Jones DS, Burton GJ, Yung HW. Placental endoplasmic reticulum stress negatively regulates transcription of placental growth factor via ATF4 and ATF6beta: implications for the pathophysiology of human pregnancy complications. J Pathol. 2016;238(4):550–61.PubMedPubMedCentralGoogle Scholar
  36. 36.
    •• McGinnis R, et al. Variants in the fetal genome near FLT1 are associated with risk of preeclampsia. Nat Genet. 2017;49(8):1255–60. First group to identify a significant association between genetic variants near the FLT-1 gene and PE development in a Finnish population. PubMedGoogle Scholar
  37. 37.
    Rajakumar A, Cerdeira AS, Rana S, Zsengeller Z, Edmunds L, Jeyabalan A, et al. Transcriptionally active syncytial aggregates in the maternal circulation may contribute to circulating soluble fms-like tyrosine kinase 1 in preeclampsia. Hypertension. 2012;59(2):256–64.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Maynard S, Epstein FH, Karumanchi SA. Preeclampsia and angiogenic imbalance. Annu Rev Med. 2008;59:61–78.PubMedGoogle Scholar
  39. 39.
    Chaiworapongsa T, Romero R, Kim YM, Kim GJ, Kim MR, Espinoza J, et al. Plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated prior to the clinical diagnosis of pre-eclampsia. J Matern Fetal Neonatal Med. 2005;17(1):3–18.PubMedGoogle Scholar
  40. 40.
    Hertig A, et al. Maternal serum sFlt1 concentration is an early and reliable predictive marker of preeclampsia. Clin Chem. 2004;50(9):1702–3.PubMedGoogle Scholar
  41. 41.
    Govender N, Naicker T, Moodley J. Maternal imbalance between pro-angiogenic and anti-angiogenic factors in HIV-infected women with pre-eclampsia. Cardiovasc J Afr. 2013;24(5):174–9.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006;355(10):992–1005.PubMedGoogle Scholar
  43. 43.
    Robinson CJ, Johnson DD, Chang EY, Armstrong DM, Wang W. Evaluation of placenta growth factor and soluble Fms-like tyrosine kinase 1 receptor levels in mild and severe preeclampsia. Am J Obstet Gynecol. 2006;195(1):255–9.PubMedGoogle Scholar
  44. 44.
    Chaiworapongsa T, Romero R, Espinoza J, Bujold E, Mee Kim Y, Gonçalves LF, et al. Evidence supporting a role for blockade of the vascular endothelial growth factor system in the pathophysiology of preeclampsia. Young Investigator Award. Am J Obstet Gynecol. 2004;190(6):1541–7 discussion 1547-50.PubMedGoogle Scholar
  45. 45.
    Gallardo-Vara E, et al. Soluble endoglin regulates expression of angiogenesis-related proteins and induction of arteriovenous malformations in a mouse model of hereditary hemorrhagic telangiectasia. Dis Models Mech. 2018;11(9). Scholar
  46. 46.
    Ermini L, Ausman J, Melland-Smith M, Yeganeh B, Rolfo A, Litvack ML, et al. A single sphingomyelin species promotes exosomal release of endoglin into the maternal circulation in preeclampsia. Sci Rep. 2017;7(1):12172.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Govender N, Naicker T, Rajakumar A, Moodley J. Soluble fms-like tyrosine kinase-1 and soluble endoglin in HIV-associated preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2013;170(1):100–5.PubMedGoogle Scholar
  48. 48.
    Venkatesha S, Toporsian M, Lam C, Hanai JI, Mammoto T, Kim YM, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12(6):642–9.PubMedGoogle Scholar
  49. 49.
    Noori M, Donald AE, Angelakopoulou A, Hingorani AD, Williams DJ. Prospective study of placental angiogenic factors and maternal vascular function before and after preeclampsia and gestational hypertension. Circulation. 2010;122(5):478–87.PubMedGoogle Scholar
  50. 50.
    Yelumalai S, Muniandy S, Zawiah Omar S, Qvist R. Pregnancy-induced hypertension and preeclampsia: levels of angiogenic factors in Malaysian women. J Clin Biochem Nutr. 2010;47(3):191–7.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Romero R, Nien JK, Espinoza J, Todem D, Fu W, Chung H, et al. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J Matern Fetal Neonatal Med. 2008;21(1):9–23.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Chaiworapongsa T, Romero R, Whitten AE, Korzeniewski SJ, Chaemsaithong P, Hernandez-Andrade E, et al. The use of angiogenic biomarkers in maternal blood to identify which SGA fetuses will require a preterm delivery and mothers who will develop pre-eclampsia. J Matern Fetal Neonatal Med. 2016;29(8):1214–28.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol. 2006;7(5):359–71.PubMedGoogle Scholar
  54. 54.
    Goksu Erol AY, Nazli M, Yildiz SE. Significance of platelet endothelial cell adhesion molecule-1 (PECAM-1) and intercellular adhesion molecule-1 (ICAM-1) expressions in preeclamptic placentae. Endocrine. 2012;42(1):125–31.PubMedGoogle Scholar
  55. 55.
    Thakoordeen S, Moodley J, Naicker T. Serum levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and soluble vascular endothelial growth factor receptor (sVEGFR)-1 and -2 in HIV associated preeclampsia. Hypertens Pregnancy. 2017;36(2):168–74.PubMedGoogle Scholar
  56. 56.
    Lyall F, Greer IA, Boswell F, Young A, Macara LM, Jeffers MD. Expression of cell adhesion molecules in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth retardation. Placenta. 1995;16(7):579–87.PubMedGoogle Scholar
  57. 57.
    Kappou D, et al. Role of the angiopoietin/tie system in pregnancy (review). Exp Ther Med. 2015;9(4):1091–6.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Thomas M, Augustin HG. The role of the angiopoietins in vascular morphogenesis. Angiogenesis. 2009;12(2):125–37.PubMedGoogle Scholar
  59. 59.
    Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, et al. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell. 1996;87(7):1161–9.PubMedGoogle Scholar
  60. 60.
    Hirokoshi K, et al. Increase of serum angiopoietin-2 during pregnancy is suppressed in women with preeclampsia. Am J Hypertens. 2005;18(9 Pt 1):1181–8.PubMedGoogle Scholar
  61. 61.
    Hirokoshi K, Maeshima Y, Kobayashi K, Matsuura E, Sugiyama H, Yamasaki Y, et al. Elevated serum sFlt-1/Ang-2 ratio in women with preeclampsia. Nephron Clin Pract. 2007;106(1):c43–50.PubMedGoogle Scholar
  62. 62.
    Sung JF, Fan X, Dhal S, Dwyer BK, Jafari A, el-Sayed YY, et al. Decreased circulating soluble Tie2 levels in preeclampsia may result from inhibition of vascular endothelial growth factor (VEGF) signaling. J Clin Endocrinol Metab. 2011;96(7):E1148–52.PubMedPubMedCentralGoogle Scholar
  63. 63.
    Gotsch F, Romero R, Kusanovic JP, Chaiworapongsa T, Dombrowski M, Erez O, et al. Preeclampsia and small-for-gestational age are associated with decreased concentrations of a factor involved in angiogenesis: soluble Tie-2. J Matern Fetal Neonatal Med. 2008;21(6):389–402.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Leinonen E, Wathén KA, Alfthan H, Ylikorkala O, Andersson S, Stenman UH, et al. Maternal serum angiopoietin-1 and -2 and tie-2 in early pregnancy ending in preeclampsia or intrauterine growth retardation. J Clin Endocrinol Metab. 2010;95(1):126–33.PubMedGoogle Scholar
  65. 65.
    Mbhele N, Moodley J, Naicker T. Role of angiopoietin-2, endoglin, and placental growth factor in HIV-associated preeclampsia. Hypertens Pregnancy. 2017;36(3):240–6.PubMedGoogle Scholar
  66. 66.
    Scharfe-Nugent A, Corr SC, Carpenter SB, Keogh L, Doyle B, Martin C, et al. TLR9 provokes inflammation in response to fetal DNA: mechanism for fetal loss in preterm birth and preeclampsia. J Immunol. 2012;188(11):5706–12.PubMedGoogle Scholar
  67. 67.
    Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol. 2002;20:709–60.PubMedGoogle Scholar
  68. 68.
    He B, Yang X, Li Y, Huang D, Xu X, Yang W, et al. TLR9 (toll-like receptor 9) agonist suppresses angiogenesis by differentially regulating VEGFA (vascular endothelial growth factor a) and sFLT1 (soluble vascular endothelial growth factor receptor 1) in preeclampsia. Hypertension. 2018;71(4):671–80.PubMedGoogle Scholar
  69. 69.
    Panda B, et al. Dendritic cells in the circulation of women with preeclampsia demonstrate a pro-inflammatory bias secondary to dysregulation of TLR receptors. J Reprod Immunol. 2012;94(2):210–5.PubMedGoogle Scholar
  70. 70.
    Pineda A, Verdin-Terán SL, Camacho A, Moreno-Fierros L. Expression of toll-like receptor TLR-2, TLR-3, TLR-4 and TLR-9 is increased in placentas from patients with preeclampsia. Arch Med Res. 2011;42(5):382–91.PubMedGoogle Scholar
  71. 71.
    Ahmad S, Ahmed A. Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia. Circ Res. 2004;95(9):884–91.PubMedGoogle Scholar
  72. 72.
    Yang J, et al. Racial-ethnic differences in midtrimester maternal serum levels of angiogenic and antiangiogenic factors. Am J Obstet Gynecol. 2016;215(3):359.e1–359.e3599.Google Scholar
  73. 73.
    Mijal RS, et al. Midpregnancy levels of angiogenic markers in relation to maternal characteristics. Am J Obstet Gynecol. 2011;204(3):244.e1–12.Google Scholar
  74. 74.
    Poon LC, et al. First-trimester prediction of hypertensive disorders in pregnancy. Hypertension. 2009;53(5):812–8.PubMedGoogle Scholar
  75. 75.
    Akolekar R, Zaragoza E, Poon LCY, Pepes S, Nicolaides KH. Maternal serum placental growth factor at 11 + 0 to 13 + 6 weeks of gestation in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol. 2008;32(6):732–9.PubMedGoogle Scholar
  76. 76.
    Arasteh K, Hannah A. The role of vascular endothelial growth factor (VEGF) in AIDS-related Kaposi’s sarcoma. Oncologist. 2000;5(Suppl 1):28–31.PubMedGoogle Scholar
  77. 77.
    Pore N, Gupta AK, Cerniglia GJ, Maity A. HIV protease inhibitors decrease VEGF/HIF-1alpha expression and angiogenesis in glioblastoma cells. Neoplasia. 2006;8(11):889–95.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Foreman K, Kaposi's sarcoma: The role of HHV-8 and HIV-1 in pathogenesis. Expert Rev Mol Med. 2001;1:1–17.Google Scholar
  79. 79.
    Guo D, et al. Therapeutic angiogenesis of Chinese herbal medicines in ischemic heart disease: A review. Front Pharmacol. 2018;9:428.Google Scholar
  80. 80.
    Dhawan S, et al. Human immunodeficiency virus-1-tat protein induces the cell surface expression of endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in human endothelial cells. Blood. 1997;90(4):1535–44.PubMedGoogle Scholar
  81. 81.
    Liu K, Chi DS, Li C, Hall HK, Milhorn DM, Krishnaswamy G. HIV-1 tat protein-induced VCAM-1 expression in human pulmonary artery endothelial cells and its signaling. Am J Physiol Lung Cell Mol Physiol. 2005;289(2):L252–60.PubMedGoogle Scholar
  82. 82.
    Munshi N, Groopman JE, Gill PS, Ganju RK. C-Src mediates Mitogenic signals and associates with cytoskeletal proteins upon vascular endothelial growth factor stimulation in Kaposi’s sarcoma cells. J Immunol. 2000;164(3):1169–74.PubMedGoogle Scholar
  83. 83.
    Kalumba VM, Moodley J, Naidoo TD. Is the prevalence of pre-eclampsia affected by HIV/AIDS? A retrospective case-control study. Cardiovasc J Afr. 2013;24(2):24–7.PubMedPubMedCentralGoogle Scholar
  84. 84.
    Fourie C, van Rooyen J, Pieters M, Conradie K, Hoekstra T, Schutte A. Is HIV-1 infection associated with endothelial dysfunction in a population of African ancestry in South Africa? Cardiovasc J Afr. 2011;22(3):134–40.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Sansone M, Sarno L, Saccone G, Berghella V, Maruotti GM, Migliucci A, et al. Risk of preeclampsia in human immunodeficiency virus-infected pregnant women. Obstet Gynecol. 2016;127(6):1027–32.PubMedGoogle Scholar
  86. 86.
    Landi B, Bezzeccheri V, Guerra B, Piemontese M, Cervi F, Cecchi L, et al. HIV infection in pregnancy and the risk of gestational hypertension and preeclampsia. World J Cardiovasc Dis. 2014;4:257–67.Google Scholar
  87. 87.
    Machado ES, Krauss MR, Megazzini K, Coutinho CM, Kreitchmann R, Melo VH, et al. Hypertension, preeclampsia and eclampsia among HIV-infected pregnant women from Latin America and Caribbean countries. J Infect. 2014;68(6):572–80.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Hall D, Gebhardt S, Theron G, Grové D. Pre-eclampsia and gestational hypertension are less common in HIV infected women. Pregnancy Hypertens. 2014;4(1):91–6.PubMedGoogle Scholar
  89. 89.
    Lu J, et al. A follow-up study of women with a history of severe preeclampsia: relationship between metabolic syndrome and preeclampsia. Chin Med J. 2011;124(5):775–9.PubMedGoogle Scholar
  90. 90.
    Akolekar R, Syngelaki A, Sarquis R, Zvanca M, Nicolaides KH. Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11-13 weeks. Prenat Diagn. 2011;31(1):66–74.PubMedGoogle Scholar
  91. 91.
    Kenny LC, Black MA, Poston L, Taylor R, Myers JE, Baker PN, et al. Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the screening for pregnancy endpoints (SCOPE) international cohort study. Hypertension. 2014;64(3):644–52.PubMedGoogle Scholar
  92. 92.
    Zeisler H, Llurba E, Chantraine F, Vatish M, Cathrine Staff A, Sennström M, et al. Predictive value of the sFlt-1: PlGF ratio in women with suspected preeclampsia. Obstet Anesth Dig. 2016;36(3):145–6.Google Scholar
  93. 93.
    Stepan H, Herraiz I, Schlembach D, Verlohren S, Brennecke S, Chantraine F, et al. Implementation of the sFlt-1/PlGF ratio for prediction and diagnosis of pre-eclampsia in singleton pregnancy: implications for clinical practice. Ultrasound Obstet Gynecol. 2015;45(3):241–6.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Perales A, et al. O23. STEPS (study of early preeclampsia in Spain): sFlt-1/PlGF for the prediction of early-onset preeclampsia in singleton pregnancies. Pregnancy Hypertens: An Int J Women’s Cardiovasc Health. 2015;5(3):216–8.Google Scholar
  95. 95.
    Verlohren S, et al. The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol. 2012;206(1):58.e1–8.Google Scholar
  96. 96.
    Salahuddin S, et al. Diagnostic utility of soluble fms-like tyrosine kinase 1 and soluble endoglin in hypertensive diseases of pregnancy. Am J Obstet Gynecol. 2007;197(1):28.e1–6.Google Scholar
  97. 97.
    Schlembach D, Hund M, Schroer A, Wolf C. Economic assessment of the use of the sFlt-1/PlGF ratio test to predict preeclampsia in Germany. BMC Health Serv Res. 2018;18:603.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Vatish M, Strunz-McKendry T, Hund M, Allegranza D, Wolf C, Smare C. sFlt-1/PlGF ratio test for pre-eclampsia: an economic assessment for the UK. Ultrasound Obstet Gynecol. 2016;48(6):765–71.PubMedPubMedCentralGoogle Scholar
  99. 99.
    Hund M, Allegranza D, Schoedl M, Dilba P, Verhagen-Kamerbeek W, Stepan H. Multicenter prospective clinical study to evaluate the prediction of short-term outcome in pregnant women with suspected preeclampsia (PROGNOSIS): study protocol. BMC Pregnancy Childbirth. 2014;14:324.PubMedPubMedCentralGoogle Scholar
  100. 100.
    Frusca T, Gervasi MT, Paolini D, Dionisi M, Ferre F, Cetin I. Budget impact analysis of sFlt-1/PlGF ratio as prediction test in Italian women with suspected preeclampsia. J Matern Fetal Neonatal Med. 2017;30(18):2166–73.PubMedGoogle Scholar
  101. 101.
    Thadhani R. Inching towards a targeted therapy for preeclampsia. Hypertension. 2010;55(2):238–40.PubMedGoogle Scholar
  102. 102.
    Thadhani R, Hagmann H, Schaarschmidt W, Roth B, Cingoez T, Karumanchi SA, et al. Removal of soluble fms-like tyrosine kinase-1 by dextran sulfate apheresis in preeclampsia. J Am Soc Nephrol. 2016;27(3):903–13.PubMedGoogle Scholar
  103. 103.
    Easterling TR. Apheresis to treat preeclampsia: insights, opportunities and challenges. J Am Soc Nephrol: JASN. 2016;27(3):663–5.PubMedGoogle Scholar
  104. 104.
    Costantine MM, Cleary K. Pravastatin for the prevention of preeclampsia in high-risk pregnant women. Obstet Gynecol. 2013;121(2 Pt 1):349–53.PubMedGoogle Scholar
  105. 105.
    Ramma W, Ahmed A. Therapeutic potential of statins and the induction of heme oxygenase-1 in preeclampsia. J Reprod Immunol. 2014;101-102:153–60.PubMedPubMedCentralGoogle Scholar
  106. 106.
    Ahmed A. New insights into the etiology of preeclampsia: identification of key elusive factors for the vascular complications. Thromb Res. 2011;127(Suppl 3):S72–5.PubMedGoogle Scholar
  107. 107.
    Muchova L, Wong RJ, Hsu M, Morioka I, Vitek L, Zelenka J, et al. Statin treatment increases formation of carbon monoxide and bilirubin in mice: a novel mechanism of in vivo antioxidant protection. Can J Physiol Pharmacol. 2007;85(8):800–10.PubMedGoogle Scholar
  108. 108.
    Khalil A, et al. Effect of antihypertensive therapy with alpha-methyldopa on uterine artery Doppler in pregnancies with hypertensive disorders. Ultrasound Obstet Gynecol. 2010;35(6):688–94.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Sayuri Padayachee
    • 1
    Email author
  • Jagidesa Moodley
    • 2
  • Thajasvarie Naicker
    • 1
  1. 1.Optics and Imaging Centre, Doris Duke Medical Research Institute, Nelson R. Mandela School of MedicineUniversity of KwaZulu-NatalDurbanSouth Africa
  2. 2.Women’s Health and HIV Research Group, Department of Obstetrics and Gynecology, Nelson R. Mandela School of MedicineUniversity of KwaZulu-NatalDurbanSouth Africa

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