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Management of VEGF-Targeted Therapy-Induced Hypertension

  • Antihypertensive Agents: Mechanisms of Drug Action (ME Ernst, Section Editor)
  • Published:
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Abstract

Purpose of Review

From a physiological point of view, VEGFs (vascular endothelial growth factors) and their receptors (VEGFR) play a critical role in vascular development angiogenesis, endothelial function, and vascular tone. On the pathological side, VEGF–VEGFR signaling may induce dysregulated angiogenesis, which contributes to the growth and to the spread of tumors, being essential for neoplastic proliferation and invasion.

Recent Findings

Pharmacological inhibition of VEGF–VEGFR is now a cornerstone in the treatment of many malignancies; however, treatment with VEGF inhibitors is commonly associated with an increase in blood pressure values. This side effect is strictly connected with the mechanism of action of these medications and might represent an index of therapy efficacy.

Summary

The optimal management of this form of hypertension is, at present, not clear. Calcium channel blockers and renin-angiotensin system inhibitors probably represent the most appropriate classes of hypertensive dugs for the treatment of this condition; however, no conclusive data are presently available.

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References

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

  1. Svilaas T, Lefrandt JD, Gietema JA, Kamphuisen PW. Long-term arterial complications of chemotherapy in patients with cancer. Thromb Res. 2016;140S1:S109–18.

    Article  CAS  Google Scholar 

  2. De Santis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64:252–71.

    Article  Google Scholar 

  3. Strumberg D, Brugge S, Korn MW, et al. Evaluation of long-term toxicity in patients after cisplatin-based chemotherapy for non-seminomatous testicular cancer. Ann Oncol. 2002;13:229–36.

    Article  PubMed  CAS  Google Scholar 

  4. De Vos F, Nuver J, Willemse P. Long-term survivors of ovarian malig- nancies after cisplatin-based chemotherapy: cardiovascular risk factors and signs of vascular damage. Eur J Cancer. 2004;40:696–700.

    Article  PubMed  Google Scholar 

  5. Yeh ET, Tong AT, Lenihan DJ, Yusuf SW, Swafford J, Champion C, et al. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation. 2004;109:3122–31.

    Article  PubMed  Google Scholar 

  6. Barrett-Lee PJ, Dixon JM, Farrell C, Jones A, Leonard R, Murray N, et al. Expert opinion on the use of anthracyclines in patients with advanced breast cancer at cardiac risk. Ann Oncol. 2009;20:816–27.

    Article  PubMed  CAS  Google Scholar 

  7. Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, et al. Chronic health conditions in adult survivors of childhood cancer—Childhood Cancer Survivor Study. N Engl J Med. 2006;355:1572–82.

    Article  PubMed  CAS  Google Scholar 

  8. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.

    Article  PubMed  CAS  Google Scholar 

  9. Ranpura V, Pulipati B, Chu D, Zhu X, Wu S. Increased risk of high-grade hypertension with bevacizumab in cancer patients: a meta-analysis. Am J Hypertens. 2010;23:460–8.

    Article  PubMed  CAS  Google Scholar 

  10. Allen JA, Adlakha A, Bergethon PR. Reversible posterior leukoencephalopathy syndrome after bevacizumab/FOLFIRI regimen for metastatic colon cancer. Arch Neurol. 2006;63:1475–8.

    Article  PubMed  Google Scholar 

  11. Ozcan C, Wong SJ, Hari P. Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med. 2006;354:980–2.

    Article  PubMed  Google Scholar 

  12. Zhu X, Wu S, Dahut WL, Parikh CR. Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am J Kidney Dis. 2007;49:186–93.

    Article  PubMed  CAS  Google Scholar 

  13. Faruque LI, Lin M, Battistella M, Wiebe N, Reiman T, Hemmelgarn B, et al. Systematic review of the risk of adverse outcomes associated with vascular endothelial growth factor inhibitors for the treatment of cancer. PLoS One. 2014;9(7):e101145.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Zhu X, Stergiopoulos K, Wu S. Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. Acta Oncol. 2009;48:9–17.

    Article  PubMed  CAS  Google Scholar 

  15. Qi WX, Shen Z, Lin F, Sun YJ, Min DL, Tang LN, et al. Incidence and risk of hypertension with vandetanib in cancer patients: a systematic review and meta-analysis of clinical trials. Br J Clin Pharmacol. 2013;75:919–30.

    Article  PubMed  CAS  Google Scholar 

  16. Qi WX, Lin F, Sun YJ, Tang LN, He AN, Yao Y, et al. Incidence and risk of hypertension with pazopanib in patients with cancer: a meta-analysis. Cancer Chemother Pharmacol. 2013;71:431–9.

    Article  PubMed  CAS  Google Scholar 

  17. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.

    Article  PubMed  CAS  Google Scholar 

  18. Rixe O, Billemont B, Izzedine H. Hypertension as a predictive factor of Sunitinib activity. Ann Oncol. 2007;18:1117.

    Article  PubMed  CAS  Google Scholar 

  19. Fukuda N, Takahari D, Wakatsuk T. Early hypertension is associated with better clinical outcomes in gastric cancer patients treated with ramucirumab plus paclitaxel. Oncotarget. 2018;9:15219–27.

    PubMed  PubMed Central  Google Scholar 

  20. Hurwitz HI, Douglas PS, Middleton JP, Sledge GW, Johnson DH, Reardon DA, et al. Analysis of early hypertension and clinical outcome with bevacizumab: results from seven phase III studies. Oncologist. 2013;18:273–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Harper SJ, Bates DO. VEGF-A splicing: the key to anti-angiogenic therapeutics? Nat Rev Cancer. 2008;8:880–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Takahashi S. Vascular endothelial growth factor (VEGF), VEGF receptors and their inhibitors for antiangiogenic tumor therapy. Biol Pharm Bull. 2011;34:1785–8.

    Article  PubMed  CAS  Google Scholar 

  23. Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature. 2005;438:967–74.

    Article  PubMed  CAS  Google Scholar 

  24. Storkebaum E, Ruiz de Almodovar C, Meens M, Zacchigna S, Mazzone M, Vanhoutte G, et al. Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery. Circulation. 2010;122:273–81.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Sela S, Itin A, Natanson-Yaron S, Greeneld C, Goldman-Wohl D, Yagel S, et al. A novel human-specific soluble vascular endothelial growth factor receptor 1: cell-type-specific splicing and implications to vascular endothelial growth factor homeostasis and preeclampsia. Circ Res. 2008;102:1566–74.

    Article  PubMed  CAS  Google Scholar 

  27. Safran M, Kaelin WG Jr. HIF hydroxylation and the mammalian oxygen-sensing pathway. J Clin Invest. 2003;111:779–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182–6.

    Article  PubMed  CAS  Google Scholar 

  29. Morabito A, De Maio E, Di Maio M, Normanno N, Perrone F. Tyrosine kinase inhibitors of vascular endothelial growth factor receptors in clinical trials: current status and future directions. Oncologist. 2006;11:753–64.

    Article  PubMed  CAS  Google Scholar 

  30. Force T, Krause DS, Van Etten RA. Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat Rev Cancer. 2007;7:332–44.

    Article  PubMed  CAS  Google Scholar 

  31. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.

    Article  PubMed  CAS  Google Scholar 

  32. Spratlin JL, Cohen RB, Eadens M, Gore L, Camidge DR, Diab S, et al. Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol. 2010;28:780–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Syed YY, McKeage K. Aflibercept: a review in metastatic colorectal cancer. Drugs. 2015;75:1435–45.

    Article  PubMed  CAS  Google Scholar 

  34. •• de Jesus-Gonzalez N, Robinson E, Moslehi J, Humphreys BD. Management of antiangiogenic therapy-induced hypertension. Hypertension. 2012;60:607–15. A comprehensive review, taking into account available data about the development and management of hypertension during treatment with antiangiogenic drugs.

    Article  PubMed  CAS  Google Scholar 

  35. •• Lankhorst S, Kappers MH, van Esch JH, Danser AH, van den Meiracker AH. Mechanism of hypertension and proteinuria during angiogenesis inhibition: evolving role of endothelin-1. J Hypertens. 2013;31:444–54. An updated review dealing with mechanism underlying the development of hypertension and proteinuria during treatment with antiangiogenic drugs, again focusing on the possible role of endothelin-1.

    Article  PubMed  CAS  Google Scholar 

  36. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999;399:601–5.

    Article  PubMed  CAS  Google Scholar 

  37. 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;274:33057–63.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  39. 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;56:1131–6.

    Article  PubMed  CAS  Google Scholar 

  40. 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;61:1060–5.

    Article  PubMed  CAS  Google Scholar 

  41. Thijs AM, van Herpen CM, Verweij V, Pertijs J, van den Broek PH, van der Graaf WT, et al. Impaired endothelium-dependent vasodilation does not initiate the development of sunitinib-associated hypertension. J Hypertens. 2015;33:2075–82.

    Article  PubMed  CAS  Google Scholar 

  42. 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;58:295–302.

    Article  PubMed  CAS  Google Scholar 

  43. 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;56:675–81.

    Article  PubMed  CAS  Google Scholar 

  44. Kappers MH, de Beer VJ, Zhou Z, Danser AH, Sleijfer S, Duncker DJ, et al. Sunitinib-induced systemic vasoconstriction in swine is endothelin mediated and does not involve nitric oxide or oxidative stress. Hypertension. 2012;59:151–7.

    Article  PubMed  CAS  Google Scholar 

  45. de Jesus-Gonzalez N, Robinson E, Penchev R, von Mehren M. Regorafenib induces rapid and reversible changes in plasma nitric oxide and endothelin-1. Am J Hypertens. 2012;25:1118–23.

    Article  PubMed  CAS  Google Scholar 

  46. Lankhorst S, Kappers MH, van Esch JH, Smedts FM, Sleijfer S, Mathijssen RH, et al. Treatment of hypertension and renal injury induced by the angiogenesis inhibitor sunitinib: preclinical study. Hypertension. 2014;64:1282–9.

    Article  PubMed  CAS  Google Scholar 

  47. Agabiti-Rosei E, Rizzoni D. Microvascular structure as a prognostically relevant endpoint. J Hypertens. 2017;35:914–21.

    Article  PubMed  CAS  Google Scholar 

  48. Rizzoni D, Paini A, Salvetti M, Rossini C, De Ciuceis C, Agabiti-Rosei C, et al. Inhibitors of angiogenesis and blood pressure. Curr Cardiovasc Risk Rep. 2013;7:244–7.

    Article  Google Scholar 

  49. Mourad JJ d, Guetz G, Debbabi H, Levy BI. Blood pressure rise following angiogenesis inhibition by bevacizumab: a crucial role for microcirculation. Ann Oncol. 2008;19:927–34.

    Article  PubMed  Google Scholar 

  50. Steeghs N, Gelderblom H, Roodt JO, Christensen O, Rajagopalan P, Hovens M, et al. Hypertension and rarefaction during treatment with telatinib, a small molecule angiogenesis inhibitor. Clin Cancer Res. 2008;14:3470–6.

    Article  PubMed  CAS  Google Scholar 

  51. Chen DD, Dong YG, Yuan H, Chen AF. Endothelin 1 activation of endothelin A receptor/NADPH oxidase pathway and diminished anti- oxidants critically contribute to endothelial progenitor cell reduction and dysfunction in salt-sensitive hypertension. Hypertension. 2012;59:1037–43.

    Article  PubMed  CAS  Google Scholar 

  52. Neves KB, Rios FJ, van der Mey L, Alves-Lopes R, Cameron AC, Volpe M, et al. VEGFR (vascular endothelial growth factor receptor) inhibition induces cardiovascular damage via redox-sensitive processes. Hypertension. 2018;71:638–47.

    Article  PubMed  CAS  Google Scholar 

  53. •• Touyz RM, Lang NN, Herrmann J, van den Meiracker AH, Danser AHJ. Recent advances in hypertension and cardiovascular toxicities with vascular endothelial growth factor inhibition. Hypertension. 2017;70:220–6. A very recent contribution that provides an up- to-date assessment of the “state of the art.”

    Article  PubMed  CAS  Google Scholar 

  54. Gu JW, Manning RD Jr, Young E, Shparago M, Sartin B, Bailey AP. Vascular endothelial growth factor receptor inhibitor enhances dietary salt-induced hypertension in Sprague-Dawley rats. Am J Physiol Regul Integr Comp Physiol. 2009;297:R142–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Lankhorst S, Baelde HJ, Clahsen-van Groningen MC, Smedts FM, Danser AH, van den Meiracker AH. Effect of high salt diet on blood pressure and renal damage during vascular endothelial growth factor inhibition with sunitinib. Nephrol Dial Transplant. 2016;31:914–21.

    Article  PubMed  CAS  Google Scholar 

  56. •• Boursiquot BC, Zabor EC, Glezerman IG, Jaimes EA. Hypertension and VEGF (vascular endothelial growth factor) receptor tyrosine kinase inhibition: effects on renal function. Hypertension. 2017. https://doi.org/10.1161/HYPERTENSIONAHA.117.09275. This recent interesting paper provides evidence that the use of VEGF tyrosine kinase inhibitors does not adversely affect long-term renal function.

  57. Curwen JO, Musgrove HL, Kendrew J, Richmond GH, Ogilvie DJ, Wedge SR. Inhibition of vascular endothelial growth factor-a signaling induces hypertension: examining the effect of cediranib (recentin; azd2171) treatment on blood pressure in rat and the use of concomitant antihypertensive therapy. Clin Cancer Res. 2008;14:3124–31.

    Article  PubMed  CAS  Google Scholar 

  58. • Moslehi J, Pandey AK, Cardio-Oncology BN. Vascular endothelial growth factor inhibitors, salt, and macrophages: a complicated interaction. Hypertension. 2017;69:785–6. An interesting editorial comment on reference 59.

    Article  PubMed  CAS  Google Scholar 

  59. Lankhorst S, Severs D, Markó L, Rakova N, Titze J, Müller DN, et al. Salt sensitivity of angiogenesis inhibition-induced blood pressure rise: role of interstitial sodium accumulation? Hypertension. 2017;69:919–26.

    Article  PubMed  CAS  Google Scholar 

  60. Maitland ML, Bakris GL, Black HR, Chen HX, Durand JB, Elliott WJ, et al. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J Natl Cancer Inst. 2010;102:596–604.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Steingart RM, Bakris GL, Chen HX, Chen MH, Force T, Ivy SP, et al. Management of cardiac toxicity in patients receiving vascular endothelial growth factor signaling pathway inhibitors. Am Heart J. 2012;163:156–63.

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. •• Cameron AC, Touyz RM, Lang NN. Vascular complications of cancer chemotherapy. Can J Cardiol. 2016;32:852–62. A landmark contribution on the issue addressed by the present review.

    Article  PubMed  Google Scholar 

  64. • Kalaitzidis RG, Elisaf MS. Uncontrolled hypertension and oncology: clinical tips. Curr Vasc Pharmacol. 2017;16:23–9. Clinical tips on the management of uncontrolled hypertension in oncology.

    Article  PubMed  CAS  Google Scholar 

  65. •• Touyz RM, Herrmann SMS, Herrmann J. Vascular toxicities with VEGF inhibitor therapies-focus on hypertension and arterial thrombotic events. J Am Soc Hypertens. 2018. J Am Soc Hypertens. 2018 Jun;12(6):409-425. https://doi.org/10.1016/j.jash.2018.03.008. A most recent contribution on the issue, also providing some practical hints.

  66. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:1269–324.

    Article  PubMed  CAS  Google Scholar 

  67. Rizzoni D, De Ciuceis C, Porteri E, Agabiti-Rosei C, Agabiti-Rosei E. Use of antihypertensive drugs in neoplastic patients. High Blood Press Cardiovasc Prev. 2017;24:127–32.

    Article  PubMed  CAS  Google Scholar 

  68. Pande A, Lombardo J, Spangenthal E, Javle M. Hypertension secondary to anti-angiogenic therapy: experience with bevacizumab. Anticancer Res. 2007;27:3465–70.

    PubMed  CAS  Google Scholar 

  69. Mir OCR, Ropert S, Cabanes L, Blanchet B, Camps S, Billemont B, et al. Treatment of bevacizumab-induced hypertension by amlodipine. Investig New Drugs. 2012;30:702–7.

    Article  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  71. Keizman D, Huang P, Eisenberger MA, Pili R, Kim JJ, Antonarakis ES, et al. Angiotensin system inhibitors and outcome of sunitinib treatment in patients with metastatic renal cell carcinoma: a retrospective examination. Eur J Cancer. 2011;47:1955–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Derosa L, Izzedine H, Albiges L, Escudier B. Hypertension and angiotensin system inhibitors in patients with metastatic renal cell carcinoma. Oncol Rev. 2016;10(2):298.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. McKay RR, Rodriguez GE, Lin X, Kaymakcalan MD, Hamnvik OP, Sabbisetti VS, et al. Angiotensin system inhibitors and survival outcomes in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2015;21:2471–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Sorich MJ, Rowland A, Kichenadasse G, Woodman RJ, Mangoni AA. Risk factors of proteinuria in renal cell carcinoma patients treated with VEGF inhibitors: a secondary analysis of pooled clinical trial data. Br J Cancer. 2016;114:1313–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Langenberg MH, van Herpen CM, De Bono J, Schellens JH, Unger C, Hoekman K, et al. Effective strategies for management of hyper tension after vascular endothelial growth factor signaling inhibition therapy: results from a phase II randomized, factorial, double-blind study of cediranib in patients with advanced solid tumors. J Clin Oncol. 2009;27:6152–9.

    Article  PubMed  CAS  Google Scholar 

  78. •• van den Meiracker AH, Danser AH. Mechanisms of hypertension and renal injury during vascular endothelial growth factor signaling inhibition. Hypertension. 2016;68:17–23. The article provides a description of the mechanisms possibly involved in the development of hypertension and renal injury during VEGF signalling inhibition.

  79. Miura S, Fujino M, Matsuo Y, Tanigawa H, Saku K. Nifedipine-induced vascular endothelial growth factor secretion from coronary smooth muscle cells promotes endothelial tube formation via the kinase insert domain-containing receptor/fetal liver kinase-1/NO pathway. Hypertens Res. 2005;28:147–53.

    Article  PubMed  CAS  Google Scholar 

  80. Miyajima A, Yazawa S, Kosaka T, Tanaka N, Shirotake S, Mizuno R, et al. Prognostic impact of renin-angiotensin system blockade on renal cell carcinoma after surgery. Ann Surg Oncol. 2015;22:3751–9.

    Article  PubMed  Google Scholar 

  81. Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, et al. Task force members. 2013 ESH/ESC guidelines for the management of arterial hypertension. The task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31:1281–357.

    Article  PubMed  CAS  Google Scholar 

  82. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71:e127–248.

    Article  PubMed  Google Scholar 

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  1. Clinica Medica, Department of Medical and Surgical Sciences, University of Brescia, c/o 2a Medicina Spedali Civili di Brescia, Piazza Spedali Civili 1, 25100, Brescia, Italy

    Stefano Caletti, Anna Paini, Maria Antonietta Coschignano, Carolina De Ciuceis, Matteo Nardin, Roberto Zulli, Maria Lorenza Muiesan, Massimo Salvetti & Damiano Rizzoni

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  1. Stefano Caletti
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Caletti, S., Paini, A., Coschignano, M.A. et al. Management of VEGF-Targeted Therapy-Induced Hypertension. Curr Hypertens Rep 20, 68 (2018). https://doi.org/10.1007/s11906-018-0871-1

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