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Abstract

The members of vascular endothelial growth factors (VEGF) are the principal regulators of angiogenesis and vascular biology. The specific growth factor of the endothelial cells is VEGF, which produces nitric oxide (NO) from endothelial cells causing vasodilation. VEGF-A, the best characterized and the most biologically active isoform, is critical for endothelial cell survival, inhibits apoptosis, increases vascular permeability, and stimulates vasodilation. VEGF-A is also a positive regulator of tumor growth and metastases. VEGF inhibitors are effective antiangiogenic agents used to treat cancer. However, hypertension is the most reported adverse effect of angiogenesis inhibitors interfering with VEGF signaling. Since VEGF stimulates vasodilation and NO, which plays a critical role in blood pressure control, VEGF may affect blood pressure regulation. Interestingly, a specific combination of polymorphisms in the VEGF gene (haplotype) is present more frequently in normotensive than in hypertensive subjects, and the same haplotype is found in subjects with higher plasma nitrite/nitrate levels (circulating markers of NO formation). This supports the hypothesis that impaired NO bioavailability contributes to clinical hypertension. Regarding hypertensive disorders of pregnancy, NO formation is inversely related to the antiangiogenic factors soluble VEGF receptor-1 (sFlt-1) and soluble endoglin levels in patients with preeclampsia, characterized by hypertension and proteinuria. Antihypertensive therapy may produce their effects by enhancing NO bioavailability, thus counteracting the impaired NO formation reported in these hypertensive disorders of pregnancy.

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References

  1. Yla-Herttuala S, Rissanen TT, Vajanto I, Hartikainen J. Vascular endothelial growth factors: biology and current status of clinical applications in cardiovascular medicine. J Am Coll Cardiol. 2007;49(10):1015–26.

    Article  PubMed  Google Scholar 

  2. Bautch VL. VEGF-directed blood vessel patterning: from cells to organism. Cold Spring Harb Perspect Med. 2012;2(9):a006452.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219(4587):983–5. New York, NY.

    Article  CAS  PubMed  Google Scholar 

  4. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989;161(2):851–8.

    Article  CAS  PubMed  Google Scholar 

  5. Robinson ES, Khankin EV, Karumanchi SA, Humphreys BD. Hypertension induced by vascular endothelial growth factor signaling pathway inhibition: mechanisms and potential use as a biomarker. Semin Nephrol. 2010;30(6):591–601.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Small HY, Montezano AC, Rios FJ, Savoia C, Touyz RM. Hypertension due to antiangiogenic cancer therapy with vascular endothelial growth factor inhibitors: understanding and managing a new syndrome. Can J Cardiol. 2014;30(5):534–43.

    Article  PubMed  Google Scholar 

  7. Lee S, Chen TT, Barber CL, Jordan MC, Murdock J, Desai S, et al. Autocrine VEGF signaling is required for vascular homeostasis. Cell. 2007;130(4):691–703.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9(6):669–76.

    Article  CAS  PubMed  Google Scholar 

  9. Yogi A, O’Connor SE, Callera GE, Tostes RC, Touyz RM. Receptor and nonreceptor tyrosine kinases in vascular biology of hypertension. Curr Opin Nephrol Hypertens. 2010;19(2):169–76.

    Article  CAS  PubMed  Google Scholar 

  10. Duval M, Le Boeuf F, Huot J, Gratton JP. Src-mediated phosphorylation of Hsp90 in response to vascular endothelial growth factor (VEGF) is required for VEGF receptor-2 signaling to endothelial NO synthase. Mol Biol Cell. 2007;18(11):4659–68.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Koch S, Tugues S, Li X, Gualandi L, Claesson-Welsh L. Signal transduction by vascular endothelial growth factor receptors. Biochem J. 2011;437(2):169–83.

    Article  CAS  PubMed  Google Scholar 

  12. Murohara T, Horowitz JR, Silver M, Tsurumi Y, Chen D, Sullivan A, et al. Vascular endothelial growth factor/vascular permeability factor enhances vascular permeability via nitric oxide and prostacyclin. Circulation. 1998;97(1):99–107.

    Article  CAS  PubMed  Google Scholar 

  13. Neagoe PE, Lemieux C, Sirois MG. Vascular endothelial growth factor (VEGF)-A165-induced prostacyclin synthesis requires the activation of VEGF receptor-1 and -2 heterodimer. J Biol Chem. 2005;280(11):9904–12.

    Article  CAS  PubMed  Google Scholar 

  14. Shibuya M. Vascular endothelial growth factor (VEGF)-Receptor2: its biological functions, major signaling pathway, and specific ligand VEGF-E. Endothelium. 2006;13(2):63–9.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Cao Y. VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs. Nat Rev Endocrinol. 2014;10(9):530–9.

    Article  CAS  PubMed  Google Scholar 

  17. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999;13(1):9–22.

    CAS  PubMed  Google Scholar 

  18. Saito T, Takeda N, Amiya E, Nakao T, Abe H, Semba H, et al. VEGF-A induces its negative regulator, soluble form of VEGFR-1, by modulating its alternative splicing. FEBS Lett. 2013;587(14):2179–85.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Sandrim VC, Palei AC, Metzger IF, Gomes VA, Cavalli RC, Tanus-Santos JE. Nitric oxide formation is inversely related to serum levels of antiangiogenic factors soluble fms-like tyrosine kinase-1 and soluble endogline in preeclampsia. Hypertension. 2008;52(2):402–7.

    Article  CAS  PubMed  Google Scholar 

  21. Bates DO. Vascular endothelial growth factors and vascular permeability. Cardiovasc Res. 2010;87(2):262–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Caro J, Morales E, Gutierrez E, Ruilope LM, Praga M. Malignant hypertension in patients treated with vascular endothelial growth factor inhibitors. J Clin Hypertens. 2013;15(3):215–6. Greenwich, Conn.

    Article  Google Scholar 

  23. Thijs AM, van Herpen CM, Sweep FC, Geurts-Moespot A, Smits P, van der Graaf WT, et al. Role of endogenous vascular endothelial growth factor in endothelium-dependent vasodilation in humans. Hypertension. 2013;61(5):1060–5.

    Article  CAS  PubMed  Google Scholar 

  24. Kieran MW, Kalluri R, Cho YJ. The VEGF pathway in cancer and disease: responses, resistance, and the path forward. Cold Spring Harb Perspect Med. 2012;2(12):a006593.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Goel HL, Mercurio AM. VEGF targets the tumour cell. Nat Rev. 2013;13(12):871–82.

    Article  CAS  Google Scholar 

  26. Hayman SR, Leung N, Grande JP, Garovic VD. VEGF inhibition, hypertension, and renal toxicity. Curr Oncol Rep. 2012;14(4):285–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Dreyfus B, Kawabata H, Gomez A. Selected adverse events in cancer patients treated with vascular endothelial growth factor inhibitors. Cancer Epidemiol. 2013;37(2):191–6.

    Article  CAS  PubMed  Google Scholar 

  28. Keefe D, Bowen J, Gibson R, Tan T, Okera M, Stringer A. Noncardiac vascular toxicities of vascular endothelial growth factor inhibitors in advanced cancer: a review. Oncologist. 2011;16(4):432–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Bair SM, Choueiri TK, Moslehi J. Cardiovascular complications associated with novel angiogenesis inhibitors: emerging evidence and evolving perspectives. Trends Cardiovasc Med. 2013;23(4):104–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Nagai A, Sado T, Naruse K, Noguchi T, Haruta S, Yoshida S, et al. Antiangiogenic-induced hypertension: the molecular basis of signaling network. Gynecol Obstet Invest. 2012;73(2):89–98.

    Article  CAS  PubMed  Google Scholar 

  31. Sunshine SB, Dallabrida SM, Durand E, Ismail NS, Bazinet L, Birsner AE, et al. Endostatin lowers blood pressure via nitric oxide and prevents hypertension associated with VEGF inhibition. Proc Natl Acad Sci U S A. 2012;109(28):11306–11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Kruzliak P, Kovacova G, Pechanova O. Therapeutic potential of nitric oxide donors in the prevention and treatment of angiogenesis-inhibitor-induced hypertension. Angiogenesis. 2013;16(2):289–95.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Bouloumie A, Schini-Kerth VB, Busse R. Vascular endothelial growth factor up-regulates nitric oxide synthase expression in endothelial cells. Cardiovasc Res. 1999;41(3):773–80.

    Article  CAS  PubMed  Google Scholar 

  34. Henry TD, Annex BH, McKendall GR, Azrin MA, Lopez JJ, Giordano FJ, et al. The VIVA trial: vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation. 2003;107(10):1359–65.

    Article  CAS  PubMed  Google Scholar 

  35. Facemire CS, Nixon AB, Griffiths R, Hurwitz H, Coffman TM. Vascular endothelial growth factor receptor 2 controls blood pressure by regulating nitric oxide synthase expression. Hypertension. 2009;54(3):652–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. des Guetz G, Uzzan B, Chouahnia K, Morere JF. Cardiovascular toxicity of anti-angiogenic drugs. Target Oncol. 2011;6(4):197–202.

    Article  PubMed  Google Scholar 

  37. Lambrechts D, Moisse M, Delmar P, Miles DW, Leighl N, Escudier B, et al. Genetic markers of bevacizumab-induced hypertension. Angiogenesis. 2014;17(3):685–94.

    CAS  PubMed  Google Scholar 

  38. Maru D, Venook AP, Ellis LM. Predictive biomarkers for bevacizumab: are we there yet? Clin Cancer Res. 2013;19(11):2824–7.

    Article  CAS  PubMed  Google Scholar 

  39. Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A, et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008;26(28):4672–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Jubb AM, Harris AL. Biomarkers to predict the clinical efficacy of bevacizumab in cancer. Lancet. 2010;11(12):1172–83.

    Article  CAS  PubMed  Google Scholar 

  41. Chow LQ, Eckhardt SG. Sunitinib: from rational design to clinical efficacy. J Clin Oncol. 2007;25(7):884–96.

    Article  CAS  PubMed  Google Scholar 

  42. Eechoute K, van der Veldt AA, Oosting S, Kappers MH, Wessels JA, Gelderblom H, et al. Polymorphisms in endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) predict sunitinib-induced hypertension. Clin Pharmacol Ther. 2012;92(4):503–10.

    CAS  PubMed  Google Scholar 

  43. Wiley KE, Davenport AP. Physiological antagonism of endothelin-1 in human conductance and resistance coronary artery. Br J Pharmacol. 2001;133(4):568–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Kappers MH, Smedts FM, Horn T, van Esch JH, Sleijfer S, Leijten F, et al. The vascular endothelial growth factor receptor inhibitor sunitinib causes a preeclampsia-like syndrome with activation of the endothelin system. Hypertension. 2011;58(2):295–302.

    Article  CAS  PubMed  Google Scholar 

  45. Kappers MH, van Esch JH, Sluiter W, Sleijfer S, Danser AH, van den Meiracker AH. Hypertension induced by the tyrosine kinase inhibitor sunitinib is associated with increased circulating endothelin-1 levels. Hypertension. 2010;56(4):675–81.

    Article  CAS  PubMed  Google Scholar 

  46. van Erp NP, Eechoute K, van der Veldt AA, Haanen JB, Reyners AK, Mathijssen RH, et al. Pharmacogenetic pathway analysis for determination of sunitinib-induced toxicity. J Clin Oncol. 2009;27(26):4406–12.

    Article  PubMed  Google Scholar 

  47. He H, Venema VJ, Gu X, Venema RC, Marrero MB, Caldwell RB. Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-Src. J Biol Chem. 1999;274(35):25130–5.

    Article  CAS  PubMed  Google Scholar 

  48. Liu MH, Jin HK, Floten HS, Yang Q, Yim AP, Furnary A, et al. Vascular endothelial growth factor-mediated endothelium-dependent relaxation is blunted in spontaneously hypertensive rats. J Pharmacol Exp Ther. 2001;296(2):473–7.

    CAS  PubMed  Google Scholar 

  49. Wei W, Jin H, Chen ZW, Zioncheck TF, Yim AP, He GW. Vascular endothelial growth factor-induced nitric oxide- and PGI2-dependent relaxation in human internal mammary arteries: a comparative study with KDR and Flt-1 selective mutants. J Cardiovasc Pharmacol. 2004;44(5):615–21.

    Article  CAS  PubMed  Google Scholar 

  50. Sandrim VC, Luizon MR, Izidoro-Toledo TC, Coelho EB, Moreno Jr H, Tanus-Santos JE. Functional VEGF haplotypes affect the susceptibility to hypertension. J Hum Hypertens. 2013;27(1):31–7.

    Article  CAS  PubMed  Google Scholar 

  51. Vyzantiadis T, Karagiannis A, Douma S, Harsoulis P, Vyzantiadis A, Zamboulis C. Vascular endothelial growth factor and nitric oxide serum levels in arterial hypertension. Clin Exp Hypertens. 2006;28(7):603–9.

    Article  CAS  PubMed  Google Scholar 

  52. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987;84(24):9265–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Thomas GD, Zhang W, Victor RG. Nitric oxide deficiency as a cause of clinical hypertension: promising new drug targets for refractory hypertension. JAMA. 2001;285(16):2055–7.

    Article  CAS  PubMed  Google Scholar 

  54. Lacchini R, Luizon MR, Gasparini S, Ferreira-Sae MC, Schreiber R, Nadruz Jr W, et al. Effect of genetic polymorphisms of vascular endothelial growth factor on left ventricular hypertrophy in patients with systemic hypertension. Am J Cardiol. 2014;113(3):491–6.

    Article  CAS  PubMed  Google Scholar 

  55. Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res. 2011;25(4):391–403.

    Article  Google Scholar 

  56. Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010;376(9741):631–44.

    Article  PubMed  Google Scholar 

  57. Ahmed R, Dunford J, Mehran R, Robson S, Kunadian V. Pre-eclampsia and future cardiovascular risk among women: a review. J Am Coll Cardiol. 2014;63(18):1815–22.

    Article  PubMed  Google Scholar 

  58. Carty DM, Delles C, Dominiczak AF. Preeclampsia and future maternal health. J Hypertens. 2010;28(7):1349–55.

    Article  CAS  PubMed  Google Scholar 

  59. Palei AC, Spradley FT, Warrington JP, George EM, Granger JP. Pathophysiology of hypertension in pre-eclampsia: a lesson in integrative physiology. Acta Physiol. 2013;208(3):224–33. Oxford, England.

    Article  CAS  Google Scholar 

  60. Warrington JP, George EM, Palei AC, Spradley FT, Granger JP. Recent advances in the understanding of the pathophysiology of preeclampsia. Hypertension. 2013;62(4):666–73.

    Article  CAS  PubMed  Google Scholar 

  61. McCarthy AL, Woolfson RG, Raju SK, Poston L. Abnormal endothelial cell function of resistance arteries from women with preeclampsia. Am J Obstet Gynecol. 1993;168(4):1323–30.

    Article  CAS  PubMed  Google Scholar 

  62. Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol. 1989;161(5):1200–4.

    Article  CAS  PubMed  Google Scholar 

  63. Demir R, Kayisli UA, Cayli S, Huppertz B. Sequential steps during vasculogenesis and angiogenesis in the very early human placenta. Placenta. 2006;27(6–7):535–9.

    Article  CAS  PubMed  Google Scholar 

  64. Ahmad S, Ahmed A. Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia. Circ Res. 2004;95(9):884–91.

    Article  CAS  PubMed  Google Scholar 

  65. Zhou Y, McMaster M, Woo K, Janatpour M, Perry J, Karpanen T, et al. Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. Am J Pathol. 2002;160(4):1405–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Sandrim VC, Palei AC, Cavalli RC, Araujo FM, Ramos ES, Duarte G, et al. Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension. Mol Hum Reprod. 2009;15(2):115–20.

    Article  CAS  PubMed  Google Scholar 

  67. Prior SJ, Hagberg JM, Paton CM, Douglass LW, Brown MD, McLenithan JC, et al. DNA sequence variation in the promoter region of the VEGF gene impacts VEGF gene expression and maximal oxygen consumption. Am J Physiol. 2006;290(5):H1848–55.

    CAS  Google Scholar 

  68. Lambrechts D, Storkebaum E, Morimoto M, Del-Favero J, Desmet F, Marklund SL, et al. VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nat Genet. 2003;34(4):383–94.

    Article  CAS  PubMed  Google Scholar 

  69. Williams DJ, Vallance PJ, Neild GH, Spencer JA, Imms FJ. Nitric oxide-mediated vasodilation in human pregnancy. Am J Physiol. 1997;272(2 Pt 2):H748–52.

    CAS  PubMed  Google Scholar 

  70. Cockell AP, Poston L. Flow-mediated vasodilatation is enhanced in normal pregnancy but reduced in preeclampsia. Hypertension. 1997;30(2 Pt 1):247–51.

    Article  CAS  PubMed  Google Scholar 

  71. Savvidou MD, Hingorani AD, Tsikas D, Frolich JC, Vallance P, Nicolaides KH. Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia. Lancet. 2003;361(9368):1511–7.

    Article  CAS  PubMed  Google Scholar 

  72. Maynard SE, Karumanchi SA. Angiogenic factors and preeclampsia. Semin Nephrol. 2011;31(1):33–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Powe CE, Levine RJ, Karumanchi SA. Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease. Circulation. 2011;123(24):2856–69.

    Article  PubMed  Google Scholar 

  74. Shibuya M. Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesis. Angiogenesis. 2006;9(4):225–30. discussion 31.

    Article  CAS  PubMed  Google Scholar 

  75. Shen BQ, Lee DY, Zioncheck TF. Vascular endothelial growth factor governs endothelial nitric-oxide synthase expression via a KDR/Flk-1 receptor and a protein kinase C signaling pathway. J Biol Chem. 1999;274(46):33057–63.

    Article  CAS  PubMed  Google Scholar 

  76. 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.

    Article  CAS  PubMed  Google Scholar 

  77. Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12(6):642–9.

    Article  CAS  PubMed  Google Scholar 

  78. Santibanez JF, Letamendia A, Perez-Barriocanal F, Silvestri C, Saura M, Vary CP, et al. Endoglin increases eNOS expression by modulating Smad2 protein levels and Smad2-dependent TGF-beta signaling. J Cell Physiol. 2007;210(2):456–68.

    Article  CAS  PubMed  Google Scholar 

  79. Podymow T, August P. Update on the use of antihypertensive drugs in pregnancy. Hypertension. 2008;51(4):960–9.

    Article  CAS  PubMed  Google Scholar 

  80. Ding Y, Vaziri ND. Nifedipine and diltiazem but not verapamil up-regulate endothelial nitric-oxide synthase expression. J Pharmacol Exp Ther. 2000;292(2):606–9.

    CAS  PubMed  Google Scholar 

  81. Taddei S, Virdis A, Ghiadoni L, Magagna A, Favilla S, Pompella A, et al. Restoration of nitric oxide availability after calcium antagonist treatment in essential hypertension. Hypertension. 2001;37(3):943–8.

    Article  CAS  PubMed  Google Scholar 

  82. Lopez-Jaramillo P, Narvaez M, Calle A, Rivera J, Jacome P, Ruano C, et al. Cyclic guanosine 3′,5′ monophosphate concentrations in pre-eclampsia: effects of hydralazine. Br J Obstet Gynaecol. 1996;103(1):33–8.

    Article  CAS  PubMed  Google Scholar 

  83. Sandrim VC, Palei AC, Luizon MR, Izidoro-Toledo TC, Cavalli RC, Tanus-Santos JE. eNOS haplotypes affect the responsiveness to antihypertensive therapy in preeclampsia but not in gestational hypertension. Pharmacogenomics J. 2010;10(1):40–5.

    Article  CAS  PubMed  Google Scholar 

  84. Luizon MR, Sandrim VC. Pharmacogenomic approaches that may guide preeclampsia therapy. Pharmacogenomics. 2013;14(6):591–3.

    Article  CAS  PubMed  Google Scholar 

  85. Williams PJ, Morgan L. The role of genetics in pre-eclampsia and potential pharmacogenomic interventions. Pharmacogenomics Pers Med. 2012;5:37–51.

    Article  CAS  Google Scholar 

  86. Sandrim VC, Palei AC, Cavalli RC, Araujo FM, Ramos ES, Duarte G, et al. eNOS haplotypes associated with gestational hypertension or preeclampsia. Pharmacogenomics. 2008;9(10):1467–73.

    Article  CAS  PubMed  Google Scholar 

  87. Sandrim VC, Palei AC, Sertorio JT, Cavalli RC, Duarte G, Tanus-Santos JE. Effects of eNOS polymorphisms on nitric oxide formation in healthy pregnancy and in pre-eclampsia. Mol Hum Reprod. 2010;16(7):506–10.

    Article  CAS  PubMed  Google Scholar 

  88. Luizon MR, Palei AC, Sandrim VC. Polymorphisms and haplotypes in candidate genes related to angiogenesis and endothelial dysfunction in preeclampsia. J Pregnancy. 2012;2012:914704.

    Article  PubMed Central  PubMed  Google Scholar 

  89. Luizon MR, Sandrim VC, Palei AC, Lacchini R, Cavalli RC, Duarte G, et al. Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy. Hypertens Res. 2012;35(9):917–21.

    Article  CAS  PubMed  Google Scholar 

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Luizon, M.R., Sandrim, V.C. (2015). Hypertension and Vascular Endothelial Growth Factors. In: Jagadeesh, G., Balakumar, P., Maung-U, K. (eds) Pathophysiology and Pharmacotherapy of Cardiovascular Disease. Adis, Cham. https://doi.org/10.1007/978-3-319-15961-4_33

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