Skip to main content
SpringerLink
Log in

Renin-Angiotensin System in Hematological Malignancies

  • Chapter
  • First Online:
The Renin Angiotensin System in Cancer, Lung, Liver and Infectious Diseases

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 25))

  • 258 Accesses

Abstract

The regular functioning of the human body is the result of interactions between numerous organs and biological systems, with the Renin-Angiotensin System (RAS) playing a crucial role in maintaining homeostasis for human existence. Though RAS is mainly known for regulation of blood pressure, however, its role in cancer development and progression has been emerging nowadays wherein this system was found to promote angiogenesis and inflammation in tumor niche. RAS comprises of numerous elements, of which angiotensin converting enzyme (ACE) is of utmost significance which converts angiotensin I (ATI) to angiotensin II (ATII), which then undergoes downstream signaling via binding to AT receptors. This signaling aids in hematopoiesis and the associated malignancies like leukemia, myeloma and lymphoma. ACE and the downstream signaling cascades upregulation could be seen in cancer models which are linked to the activation of multiple signaling events involving NF-κB, PI3K, MAPK, etc. The importance of RAS in hematological malignancies led to the exploration of RAS inhibitors for the cancer treatment. There are certain categories of RAS inhibitors which include ACE inhibitors, Angiotensin receptor blockers or renin inhibitors which have been tested in vitro either alone or in combination for therapeutics of various cancers including hematological malignancies. The local RAS and its association with cancer might opens up new avenues for investigation and development of novel therapies for hematological malignancies.

Nidhi Gupta and Shraddha Kapoor, equal contribution

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Patel S, Rauf A, Khan H, Abu- T (2017) Renin-angiotensin-aldosterone (RAAS): the ubiquitous system for homeostasis and pathologies. Biomed Pharmacother 94:317–325. https://doi.org/10.1016/j.biopha.2017.07.091

    Article  CAS  PubMed  Google Scholar 

  2. Atlas SA (2007) The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J Manag Care Pharm 13(8 Suppl B):9–20. https://doi.org/10.18553/jmcp.2007.13.s8-b.9

  3. Vargas Vargas RA, Varela Millán JM, Fajardo Bonilla E (2022) Renin-angiotensin system: Basic and clinical aspects-a general perspective. Endocrinol Diabetes Nutr 69(1):52–62. https://doi.org/10.1016/j.endinu.2021.05.012

  4. Laghlam D, Jozwiak M, Nguyen LS (2021) Renin-angiotensin-aldosterone system and immunomodulation: a state-of-the-art review. Cells 10(7):1767. https://doi.org/10.3390/cells10071767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Afsar B et al (2021) Renin-angiotensin system and cancer: epidemiology, cell signaling, genetics and epigenetics. Clin Transl Oncol 23(4):682–696. https://doi.org/10.1007/s12094-020-02488-3

    Article  CAS  PubMed  Google Scholar 

  6. George AJ, Thomas WG, Hannan RD (2010) The renin-angiotensin system and cancer: old dog, new tricks. Nat Rev Cancer 10(11):745–759. https://doi.org/10.1038/nrc2945

    Article  CAS  PubMed  Google Scholar 

  7. Sparks MA, Crowley SD, Gurley SB, Mirotsou M, Coffman TM (2014) Classical Renin-Angiotensin system in kidney physiology. Compr Physiol 4(3):1201–1228. https://doi.org/10.1002/cphy.c130040

    Article  PubMed  PubMed Central  Google Scholar 

  8. Fyhrquist F, Saijonmaa O (2008) Renin-angiotensin system revisited. J Intern Med 264(3):224–236. https://doi.org/10.1111/j.1365-2796.2008.01981.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yang J, Yang X, Gao L, Zhang J, Yi C, Huang Y (2021) The role of the renin-angiotensin system inhibitors in malignancy: a review. Am J Cancer Res 11(3):884–897

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Wegman-Ostrosky T, Soto-Reyes E, Vidal- S, Sánchez-Corona J (2015) The renin-angiotensin system meets the hallmarks of cancer. J Renin-Angiotensin Aldosterone Syst 16(2):227–233. https://doi.org/10.1177/1470320313496858

    Article  CAS  Google Scholar 

  11. Gupta N, Kumar R, Seth T, Garg B, Sharma A (2020) Targeting of stromal versican by miR-144/199 inhibits multiple myeloma by downregulating FAK/STAT3 signalling. RNA Biol 17(1):98–111. https://doi.org/10.1080/15476286.2019.1669405

    Article  CAS  PubMed  Google Scholar 

  12. Kumar R, Gupta N, null Himani, Sharma A (2018) Novel combination of tanshinone I and lenalidomide induces chemo-sensitivity in myeloma cells by modulating telomerase activity and expression of shelterin complex and its associated molecules. Mol Biol Rep 45(6):2429–2439. https://doi.org/10.1007/s11033-018-4409-z

  13. Anand V et al (2019) CD44 splice variant (CD44v3) promotes progression of urothelial carcinoma of bladder through Akt/ERK/STAT3 pathways: novel therapeutic approach. J Cancer Res Clin Oncol 145(11):2649–2661. https://doi.org/10.1007/s00432-019-03024-9

    Article  PubMed  Google Scholar 

  14. Gupta N, Kumar R, Seth T, Garg B, Sati HC, Sharma A (2019) Clinical significance of circulatory microRNA-203 in serum as novel potential diagnostic marker for multiple myeloma. J Cancer Res Clin Oncol 145(6):1601–1611. https://doi.org/10.1007/s00432-019-02896-1

    Article  CAS  PubMed  Google Scholar 

  15. Khan R, Sharma M, Kumar L, Husain SA, Sharma A (2013) Interrelationship and expression profiling of cyclooxygenase and angiogenic factors in Indian patients with multiple myeloma. Ann Hematol 92(1):101–109. https://doi.org/10.1007/s00277-012-1572-5

    Article  CAS  PubMed  Google Scholar 

  16. Rosenthal T, Gavras I (2019) Renin-angiotensin inhibition in combating malignancy: a review. Anticancer Res 39(9):4597–4602. https://doi.org/10.21873/anticanres.13639

    Article  CAS  PubMed  Google Scholar 

  17. Dolomatov S, Zukow W, Novikov N, Markaryan A, Eremeeva E (2019) Expression of the renin-angiotensin system components in oncologic diseases. Acta Clin Croat 58(2):354–364. https://doi.org/10.20471/acc.2019.58.02.21

    Article  PubMed  PubMed Central  Google Scholar 

  18. Nouet S et al (2004) Trans-inactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP. J Biol Chem 279(28):28989–28997. https://doi.org/10.1074/jbc.M403880200

    Article  CAS  PubMed  Google Scholar 

  19. Haznedaroglu IC, Beyazit Y (2013) Local bone marrow renin-angiotensin system in primitive, definitive and neoplastic haematopoiesis. Clin Sci (Lond) 124(5):307–323. https://doi.org/10.1042/CS20120300

    Article  CAS  PubMed  Google Scholar 

  20. Velez Rueda JO, Palomeque J, Mattiazzi A (2012) Early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves CaMKII. J Appl Physiol (1985), 112(12):2110–2120. https://doi.org/10.1152/japplphysiol.01383.2011

  21. Saber S, Mahmoud AAA, Goda R, Helal NS, El- E, Abdelghany RH (2018) Perindopril, fosinopril and losartan inhibited the progression of diethylnitrosamine-induced hepatocellular carcinoma in mice via the inactivation of nuclear transcription factor kappa-B. Toxicol Lett 295:32–40. https://doi.org/10.1016/j.toxlet.2018.05.036

    Article  CAS  PubMed  Google Scholar 

  22. Hardie DG, Alessi DR (2013) LKB1 and AMPK and the cancer-metabolism link - ten years after. BMC Biol 11:36. https://doi.org/10.1186/1741-7007-11-36

    Article  PubMed  PubMed Central  Google Scholar 

  23. Haznedaroğlu IC, Tuncer S, Gürsoy M (1996) A local renin-angiotensin system in the bone marrow. Med Hypotheses 46(6):507–510. https://doi.org/10.1016/s0306-9877(96)90122-x

    Article  PubMed  Google Scholar 

  24. Haznedaroglu IC, Beyazit Y (2010) Pathobiological aspects of the local bone marrow renin-angiotensin system: a review. J Renin-Angiotensin Aldosterone Syst 11(4):205–213. https://doi.org/10.1177/1470320310379876

    Article  CAS  Google Scholar 

  25. Rodgers KE, Xiong S, Steer R, diZerega GS (2000) Effect of angiotensin II on hematopoietic progenitor cell proliferation. Stem Cells 18(4):287–294. https://doi.org/10.1634/stemcells.18-4-287

  26. Albayrak M et al (2012) Elevated serum angiotensin converting enzyme levels as a reflection of bone marrow renin-angiotensin system activation in multiple myeloma. J Renin-Angiotensin Aldosterone Syst 13(2):259–264. https://doi.org/10.1177/1470320312437070

    Article  CAS  Google Scholar 

  27. Aksu S et al (2006) Over-expression of angiotensin-converting enzyme (CD 143) on leukemic blasts as a clue for the activated local bone marrow RAS in AML. Leuk Lymphoma 47(5):891–896. https://doi.org/10.1080/10428190500399250

    Article  CAS  PubMed  Google Scholar 

  28. Abali H et al (2002) Circulating and local bone marrow renin-angiotensin system in leukemic hematopoiesis: preliminary evidences. Hematology 7(2):75–82. https://doi.org/10.1080/10245330290022160

    Article  CAS  PubMed  Google Scholar 

  29. Rousseau- A et al (Oct.1998) Lisinopril, an angiotensin I-converting enzyme inhibitor, prevents entry of murine hematopoietic stem cells into the cell cycle after irradiation in vivo. Exp Hematol 26(11):1074–1079

    CAS  PubMed  Google Scholar 

  30. Rieger KJ et al (1993) Involvement of human plasma angiotensin I-converting enzyme in the degradation of the haemoregulatory peptide N-acetyl-seryl-aspartyl-lysyl-proline. Biochem J 296(Pt 2):373–378. https://doi.org/10.1042/bj2960373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rousseau A, Michaud A, Chauvet MT, Lenfant M, Corvol P (1995) The hemoregulatory peptide N-acetyl-Ser-Asp-Lys-Pro is a natural and specific substrate of the N-terminal active site of human angiotensin-converting enzyme. J Biol Chem 270(8):3656–3661. https://doi.org/10.1074/jbc.270.8.3656

    Article  CAS  PubMed  Google Scholar 

  32. Rousseau- A, Lenfant M, Potier P (Jul.1996) Catabolism of the hemoregulatory peptide N-Acetyl-Ser-Asp-Lys-Pro: a new insight into the physiological role of the angiotensin-I-converting enzyme N-active site. Bioorg Med Chem 4(7):1113–1119. https://doi.org/10.1016/0968-0896(96)00104-6

    Article  CAS  PubMed  Google Scholar 

  33. Li J, Volkov L, Comte L, Herve P, Praloran V, Charbord P (1997) Production and consumption of the tetrapeptide AcSDKP, a negative regulator of hematopoietic stem cells, by hematopoietic microenvironmental cells. Exp Hematol 25(2):140–146

    CAS  PubMed  Google Scholar 

  34. Gaudron S, Grillon C, Thierry J, Riches A, Wierenga PK, Wdzieczak-Bakala J (1999) In vitro effect of acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) analogs resistant to angiotensin I-converting enzyme on hematopoietic stem cell and progenitor cell proliferation. Stem Cells 17(2):100–106. https://doi.org/10.1002/stem.170100

    Article  CAS  PubMed  Google Scholar 

  35. Uz B et al (2013) Local hematopoietic renin-angiotensin system in myeloid versus lymphoid hematological neoplastic disorders. J Renin-Angiotensin Aldosterone Syst 14(4):308–314. https://doi.org/10.1177/1470320312464677

    Article  CAS  Google Scholar 

  36. Koca E et al (2007) Renin-angiotensin system expression in the K562 human erythroleukaemic cell line. J Renin-Angiotensin Aldosterone Syst 8(3):145–147. https://doi.org/10.3317/jraas.2007.019

    Article  CAS  Google Scholar 

  37. Koca E et al (2007) Angiotensin-converting enzyme expression of the lymphoma-associated macrophages in the lymph nodes of Hodgkin’s disease. J Natl Med Assoc 99(11):1243–1244, 1246–1247

    Google Scholar 

  38. Beyazit Y et al (2007) Overexpression of the local bone marrow renin-angiotensin system in acute myeloid leukemia. J Natl Med Assoc 99(1):57–63

    PubMed  PubMed Central  Google Scholar 

  39. Strawn WB, Richmond RS, Ann Tallant E, Gallagher PE, Ferrario CM (2004) Renin-angiotensin system expression in rat bone marrow haematopoietic and stromal cells. Br J Haematol 126(1):120–126. https://doi.org/10.1111/j.1365-2141.2004.04998.x

  40. Abali H, Güllü IH, Engin H, Haznedaroğlu IC, Erman M, Tekuzman G (2002) Old antihypertensives as novel antineoplastics: angiotensin-I-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists. Med Hypotheses 59(3):344–348. https://doi.org/10.1016/s0306-9877(02)00185-8

    Article  CAS  PubMed  Google Scholar 

  41. Mazur G, Haloń A, Wróbel T, Kuliczkowski K (2004) Macrophage/histiocytic antigen CD68 expression in neoplastic and reactive lymph nodes. Rocz Akad Med Bialymst 49(Suppl):73–75

    PubMed  Google Scholar 

  42. Radhakrishnan V et al (2017) Management of hodgkins lymphoma: ICMR consensus document. Indian J Pediatr 84(5):371–381. https://doi.org/10.1007/s12098-017-2304-6

    Article  PubMed  Google Scholar 

  43. Saka B et al (2019) The role of the local bone marrow renin-angiotensin system in multiple myeloma. Turk J Haematol 36(3):178–185. https://doi.org/10.4274/tjh.galenos.2019.2018.0420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lever AF et al (1998) Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Lancet 352(9123):179–184. https://doi.org/10.1016/S0140-6736(98)03228-0

    Article  CAS  PubMed  Google Scholar 

  45. Lucero HA, Kintsurashvili E, Marketou ME, Gavras H (2010) Cell signaling, internalization, and nuclear localization of the angiotensin converting enzyme in smooth muscle and endothelial cells. J Biol Chem 285(8):5555–5568. https://doi.org/10.1074/jbc.M109.074740

    Article  CAS  PubMed  Google Scholar 

  46. Yoshiji H, Kuriyama S, Noguchi R, Fukui H (2004) Angiotensin-I converting enzyme inhibitors as potential anti-angiogenic agents for cancer therapy. Curr Cancer Drug Targets 4(7):555–567. https://doi.org/10.2174/1568009043332790

    Article  CAS  PubMed  Google Scholar 

  47. De la Iglesia Iñigo S et al (2009) Induction of apoptosis in leukemic cell lines treated with captopril, trandolapril and losartan: a new role in the treatment of leukaemia for these agents. Leuk Res 33(6):810–816. https://doi.org/10.1016/j.leukres.2008.09.029=

  48. Stanojkovic TP, Zizak Z, Mihailovic-Stanojevic N, Petrovic T, Juranic Z (2005) Inhibition of proliferation on some neoplastic cell lines-act of carvedilol and captopril. J Exp Clin Cancer Res 24(3):387–395

    CAS  PubMed  Google Scholar 

  49. Riddiough GE et al (2022) Captopril, a renin-angiotensin system inhibitor, attenuates tumour progression in the regenerating liver following partial hepatectomy. Int J Mol Sci 23(9):5281. https://doi.org/10.3390/ijms23095281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Purclutepe O et al (2012) Enalapril-induced apoptosis of acute promyelocytic leukaemia cells involves STAT5A. Anticancer Res 32(7):2885–2893

    CAS  PubMed  Google Scholar 

  51. Fendrich V et al (2014) Enalapril and ASS inhibit tumor growth in a transgenic mouse model of islet cell tumors. Endocr Relat Cancer 21(5):813–824. https://doi.org/10.1530/ERC-14-0175

    Article  CAS  PubMed  Google Scholar 

  52. Carlos-Escalante JA, de Jesús M, Rivas-Castro A, Pichardo PS, Arce C, Wegman-Ostrosky T (2021) The use of antihypertensive drugs as coadjuvant therapy in cancer. Front Oncol 11:660943. https://doi.org/10.3389/fonc.2021.660943

    Article  PubMed  PubMed Central  Google Scholar 

  53. Fendrich V et al (2010) The angiotensin-I-converting enzyme inhibitor enalapril and aspirin delay progression of pancreatic intraepithelial neoplasia and cancer formation in a genetically engineered mouse model of pancreatic cancer. Gut 59(5):630–637. https://doi.org/10.1136/gut.2009.188961

    Article  CAS  PubMed  Google Scholar 

  54. de Araújo Júnior RF, Leitão Oliveira ALCS, de Melo Silveira RF, de Oliveira Rocha HA, de França Cavalcanti P, de Araújo AA (2015) Telmisartan induces apoptosis and regulates Bcl-2 in human renal cancer cells. Exp Biol Med (Maywood) 240(1):34–44. https://doi.org/10.1177/1535370214546267

  55. Du N et al (2012) Angiotensin II receptor type 1 blockers suppress the cell proliferation effects of angiotensin II in breast cancer cells by inhibiting AT1R signaling. Oncol Rep 27(6):1893–1903. https://doi.org/10.3892/or.2012.1720

    Article  CAS  PubMed  Google Scholar 

  56. Hu J, Zhang L-C, Song X, Lu J-R, Jin Z (2015) KRT6 interacting with notch1 contributes to progression of renal cell carcinoma, and aliskiren inhibits renal carcinoma cell lines proliferation in vitro. Int J Clin Exp Pathol 8(8):9182–9188

    PubMed  PubMed Central  Google Scholar 

  57. Georgakopoulos P et al (2019) The role of metoprolol and enalapril in the prevention of doxorubicin-induced cardiotoxicity in lymphoma patients. Anticancer Res 39(10):5703–5707. https://doi.org/10.21873/anticanres.13769

    Article  CAS  PubMed  Google Scholar 

  58. Ghasemi M et al (2019) The impact of At1r inhibition via losartan on the anti-leukaemic effects of doxorubicin in acute myeloid leukaemia. J Renin-Angiotensin Aldosterone Syst 20(2):1470320319851310. https://doi.org/10.1177/1470320319851310

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India

    Nidhi Gupta, Shraddha Kapoor & Alpana Sharma

  2. Department of Medical Oncology, BRA IRCH, All India Institute of Medical Sciences, New Delhi, India

    Aparna Sharma

Authors
  1. Nidhi Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shraddha Kapoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aparna Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alpana Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alpana Sharma .

Editor information

Editors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface Hospital, Winnipeg, MB, Canada

    Sukhwinder K. Bhullar

  2. Asper Clinical Research Institute, St. Boniface Hospital, Winnipeg, MB, Canada

    Paramjit S. Tappia

  3. Albrechtsen Research Centre, St. Boniface Hospital, Winnipeg, MB, Canada

    Naranjan S. Dhalla

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gupta, N., Kapoor, S., Sharma, A., Sharma, A. (2023). Renin-Angiotensin System in Hematological Malignancies. In: Bhullar, S.K., Tappia, P.S., Dhalla, N.S. (eds) The Renin Angiotensin System in Cancer, Lung, Liver and Infectious Diseases. Advances in Biochemistry in Health and Disease, vol 25. Springer, Cham. https://doi.org/10.1007/978-3-031-23621-1_20

Download citation

Publish with us

Policies and ethics

Search

Navigation