ADRENOMEDULLIN: BIOLOGICAL FUNCTIONS AND PROSPECTS FOR USE AS A BIOMARKER IN CLINICAL PRACTICE


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

In modern clinical practice, there is a certain shortage of objective laboratory indicators that allow us to determine the etiology of the disease or systemic inflammation syndrome, and also, based on which, it would be possible to monitor pathological processes in the body, the effectiveness of treatment or use these indicators as prognostic signs, for example, lethality. It is also necessary that the new laboratory parameters have high specificity and sensitivity, correlate with the severity of the disease, and allow early stratification of patients depending on the expected outcome in order to provide such patients with all the necessary medical care. One of these biomarkers may be adrenomedullin. It was discovered in 1993 and since then a large number of studies have been conducted that have demonstrated that adrenomedullin is widely distributed in various tissues and organs and performs a large number of biological functions. In addition, many researchers have noted that its level significantly correlates depending on the severity of the disease in patients with various pathologies. The article presents general information about adrenomedullin, its function in the body, as well as scientific data demonstrating its prognostic ability in various pathological conditions.

Full Text

Restricted Access

About the authors

Alexander A. Astapovsky

I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University]

Email: al.astapovskii@gmail.com
postgraduate student of the Department of clinical pharmacology and propaedeutics of internal diseases 119991, Moscow, 8/2 Trubetskaya Str

Vladimir N. Drozdov

I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University]

Email: vndrozdov@yandex.ru
Dr. med. habil., professor, professor of the Department of clinical pharmacology and propaedeutics of internal diseases 119991, Moscow, 8/2 Trubetskaya Str

Evgenia V. Shikh

I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University]

Email: chih@mail.ru
Dr. med. habil., professor, head of the Department of clinical pharmacology and propaedeutics of internal diseases 119991, Moscow, 8/2 Trubetskaya Str

Natalya B. Lazareva

I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University]

Email: natalia.lazareva@gmail.com
Dr. med. habil., professor of the Department of clinical pharmacology and propaedeutics of internal diseases 119991, Moscow, 8/2 Trubetskaya Str

References

  1. Schonauer R., Els-Heindl S., Beck-Sickinger A. Adrenomedullin - new perspectives of a potent peptide hormone. J Pept Sci. 2017; 23(7-8): 472-85. https://dx.doi.org/10.1002/psc.2953.
  2. Eto T., Kato J., Kitamura K. Regulation of production and secretion of adrenomedullin in the cardiovascular system. Regul Pept. 2003; 112(1-3): 61-69. https://dx.doi.org/10.1016/s0167-0115(03)00023-5.
  3. Washimine H., Asada Y., Kitamura K. et al. Immunohistochemical identification of adrenomedullin in human, rat, and porcine tissue. Histochem Cell Biol. 1995; 103(4): 251-54. https://dx.doi.org/10.1007/bf01457408.
  4. Ichiki Y., Kitamura K., Kangawa K. et al. Distribution and characterization of immunoreactive adrenomedullin in human tissue and plasma. FEBS Lett. 1994; 338(1): 6-10. https://dx.doi.org/10.1016/0014-5793(94)80106-1.
  5. Eguchi S., Hirata Y., Kano H. et al. Specific receptors for adrenomedullin in cultured rat vascular smooth muscle cells. FEBS Lett. 1994; 340(3): 226-30. https://dx.doi.org/10.1016/0014-5793(94)80143-6.
  6. Kitamura K., Sakata J., Kangawa K. et al. Cloning and characterization of cDNA encoding a precursor for human adrenomedullin. Biochem Biophys Res Commun. 1993; 194(2): 720-25. https://dx.doi.org/10.1006/bbrc.1993.1881.
  7. Gumusel B., Chang J., Hyman A., Lippton H. Adrenotensin: An ADM gene product with the opposite effects of ADM. Life Sci. 1995; 57(8): PL87-PL90. https://dx.doi.org/10.1016/0024-3205(95)02012-8.
  8. Wilkinson I., McEniery C., Bongaerts K. et al. Adrenomedullin (ADM) in the human forearm vascular bed: effect of neutral endopeptidase inhibition and comparison with proadrenomedullin NH2-terminal 20 peptide (PAMP). Br J Clin Pharmacol. 2001; 52(2): 159-64. https://dx.doi.org/10.1046/j.0306-5251.2001.1420.x.
  9. Poyner D.International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev. 2002; 54(2): 233-46. https://dx.doi.org/10.1124/pr.54.2.233.
  10. Kobayashi H., Minami S., Yamamoto R. et al. Adrenomedullin receptors in rat cerebral microvessels. Brain Res Mol Brain Res. 2000; 81(1-2): 1-6. https://dx.doi.org/10.1016/s0169-328x(00)00148-0.
  11. Hirayama N., Kitamura K., Imamura T. et al. Secretion and clearance of the mature form of adrenomedullin in humans. Life Sci. 1999; 64(26): 2505-9. https://dx.doi.org/10.1016/s0024-3205(99)00208-8.
  12. Morgenthaler N., Struck J., Alonso C., Bergmann A. Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay. Clin Chem. 2005; 51(10): 1823-29. https://dx.doi.org/10.1373/clinchem.2005.051110.
  13. McLatchie L., Fraser N., Main M. et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature. 1998; 393(6683): 333-39. https://dx.doi.org/10.1038/30666.
  14. Gibbons C., Dackor R., Dunworth W. et al. Receptor activity-modifying proteins: RAMPing up adrenomedullin signaling. Mol Endocrinol. 2007; 21(4): 783-96. https://dx.doi.org/10.1210/me.2006-0156.
  15. Coppock H., Owji A., Bloom S., Smith D. A rat skeletal muscle cell line (L6) expresses specific adrenomedullin binding sites but activates adenylate cyclase via calcitonin gene-related peptide receptors. Biochem J. 1996; 318(Pt 1): 241-45. https://dx.doi.org/10.1042/bj3180241.
  16. Shimekake Y., Nagata K., Ohta S. et al. Adrenomedullin stimulates two signal transduction pathways, cAMP accumulation and Ca2* mobilization, in bovine aortic endothelial cells. J Biol Chem. 1995; 270(9): 4412-17. https://dx.doi.org/10.1074/jbc.270.9.4412.
  17. Okumura H., Nagaya N., Itoh T. et al. Adrenomedullin infusion attenuates myocardial ischemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway. Circulation. 2004; 109(2): 242-48. https://dx.doi.org/10.1161/01.cir.0000109214.30211.7c.
  18. Nakamura M., Yoshida H., Makita S. et al. Potent and long-lasting vasodilatory effects of adrenomedullin in humans. Circulation. 1997; 95(5): 1214-21. https://dx.doi.org/10.1161/01.cir.95.5.1214.
  19. Ishimitsu T., Nishikimi T., Saito Y. et al. Plasma levels of adrenomedullin, a newly identified hypotensive peptide, in patients with hypertension and renal failure. J Clin Invest. 1994; 94(5): 2158-61. https://dx.doi.org/10.1172/jci117573.
  20. Kato J., Kitamura K., Matsui E. et al. Plasma adrenomedullin and natriuretic peptides in patients with essential or malignant hypertension. Hypertens Res. 1999; 22(1): 61-65. https://dx.doi.org/10.1291/hypres.22.61.
  21. Vincent J., Marshall J., Namendys-Silva S. et al. Assessment of the worldwide burden of critical illness: the Intensive Care Over Nations (ICON) audit. Lancet Respir Med. 2014; 2(5): 380-86. https://dx.doi.org/10.1016/s2213-2600(14)70061-x.
  22. Kita T., Kitamura K., Hashida S. et al. Plasma adrenomedullin is closely correlated with pulse wave velocity in middle-aged and elderly patients. Hypertens Res. 2003; 26(11): 887-93. https://dx.doi.org/10.1291/hypres.26.887.
  23. Kano H., Kohno M., Yasunari K. et al. Adrenomedullin as a novel antiproliferative factor of vascular smooth muscle cells. J Hypertens. 1996; 14(2): 209-13. https://dx.doi.org/10.1097/00004872-199602000-00009.
  24. Shindo T., Kurihara Y., Nishimatsu H. et al. Vascular abnormalities and elevated blood pressure in mice lacking adrenomedullin gene. Circulation. 2001; 104(16): 1964-71. https://dx.doi.org/10.1161/hc4101.097111.
  25. McGregor D., Troughton R., Frampton C. et al. Hypotensive and natriuretic actions of adrenomedullin in subjects with chronic renal impairment. Hypertension. 2001; 37(5): 1279-84. https://dx.doi.org/10.1161/01.hyp.37.5.1279.
  26. Chini E., Chini C., Bolliger C. et al. Cytoprotective effects of adrenomedullin in glomerular cell injury: Central role of cAMP signaling pathway. Kidney Int. 1997; 52(4): 917-25. https://dx.doi.org/10.1038/ki.1997.413.
  27. Kubo A., Kurioka H., Minamino N. et al. Plasma and urinary levels of adrenomedullin in chronic glomerulonephritis patients with proteinuria. Nephron. 1998; 80(2): 227-30. https://dx.doi.org/10.1159/000045172.
  28. Zudaire E., Cuttitta F., Marti-nez A. Regulation of pancreatic physiology by adrenomedullin and its binding protein. Regul Pept. 2003; 112(1-3): 121-30. https://dx.doi.org/10.1016/s0167-0115(03)00030-2.
  29. Yang B., Lippton H., Gumusel B. et al. Adrenomedullin dilates rat pulmonary artery rings during hypoxia: Role of nitric oxide and vasodilator prostaglandins. J Cardiovasc Pharmacol. 1996; 28(3): 458-62. https://dx.doi.org/10.1097/00005344-199609000-00016.
  30. Kohno M., Hanehira T., Hirata K. et al. An accelerated increase of plasma adrenomedullin in acute asthma. Metabolism. 1996; 45(11): 89 1323-25. https://dx.doi.org/10.1016/s0026-0495(96)90109-2.
  31. Kamoi H., Kanazawa H., Hirata K. et al. Adrenomedullin inhibits the secretion of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, from rat alveolar macrophages. Biochem Biophys Res Commun. 1995; 211(3): 1031-35. https://dx.doi.org/10.1006/bbrc.1995.1914.
  32. Serrano J., Alonso D., Fernandez A. et al. Adrenomedullin in the central nervous system. Microsc Res Tech. 2002; 57(2): 76-90. https://dx.doi.org/10.1002/jemt.10053.
  33. Dogan A., Suzuki Y., Koketsu N. et al.Intravenous infusion of adrenomedullin and increase in regional cerebral blood flow and prevention of ischemic brain injury after middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab. 1997; 17(1): 19-25. https://dx.doi.org/10.1097/00004647-199701000-00004.
  34. Hippenstiel S., Witzenrath M., Schmeck B. et al. Adrenomedullin reduces endothelial hyperpermeability. Circ Res. 2002; 91(7): 618-25. https://dx.doi.org/10.1161/01.res.0000036603.61868.f9.
  35. Walsh T.J., Martinez A., Peter J. et al. Antimicrobial activity of adrenomedullin and its gene-related peptides. ClinInfect Dis. 1996; 23: 877.
  36. Allaker R. An investigation into the antimicrobial effects of adrenomedullin on members of the skin, oral, respiratory tract and gut microflora. FEMS Immunol Med Microbiol. 1999; 23(4): 289-93. https://dx.doi.org/10.1016/s0928-8244(98)00148-5.
  37. Lucyk S., Taha H., Yamamoto H. et al. NMR conformational analysis of proadrenomedullin N-terminal 20 peptide, a proangiogenic factor involved in tumor growth. Biopolymers. 2006; 81(4): 295-308. https://dx.doi.org/10.1002/bip.20418.
  38. Allaker R., Grosvenor P., McAnerney D. et al. Mechanisms of adrenomedullin antimicrobial action. Peptides. 2006; 27(4): 661-66. https://dx.doi.org/10.1016/j.peptides.2005.09.003.
  39. Kato J., Kobayashi K., Etoh T. et al. Plasma adrenomedullin concentration in patients with heart failure. J Clin Endocrinol Metab. 1996; 81(1): 180-83. https://dx.doi.org/10.1210/jcem.81.1.8550749.
  40. Kobayashi K., Kitamura K., Hirayama N. et al. Increased plasma adrenomedullin in acute myocardial infarction. Am Heart J. 1996; 131(4): 676-80. https://dx.doi.org/10.1016/s0002-8703(96)90270-7.
  41. Nishikimi T., Saito Y., Kitamura K. et al. Increased plasma levels of adrenomedullin in patients with heart failure. J Am Coll Cardiol. 1995; 26(6): 1424-31. https://dx.doi.org/10.1016/0735-1097(95)00338-x.
  42. Nishida H., Horio T., Suzuki Y. et.al. Plasma adrenomedullin as an independent predictor of future cardiovascular events in high-risk patients: Comparison with C-reactive protein and adiponectin. Peptides. 2008; 29(4): 599-605. https://dx.doi.org/10.1016/j.peptides.2007.12.006.
  43. Zhang H., Tang B., Yin C. et al. Plasma adrenomedullin levels are associated with long-term outcomes of acute ischemic stroke. Peptides. 2014; 52: 44-48. https://dx.doi.org/10.1016/j.peptides.2013.11.025.
  44. Wang C., Lin H., Xu J. et al. Blood levels of adrenomedullin on admission predict outcomes after acute intracerebral hemorrhage. Peptides. 2014; 54: 27-32. https://dx.doi.org/10.1016/j.peptides.2014.01.005.
  45. Matson B., Quinn K., Lessey B. et al. Elevated levels of adrenomedullin in eutopic endometrium and plasma from women with endometriosis. Fertil Steril. 2018; 109(6): 1072-78. https://dx.doi.org/10.1016/j.fertnstert.2018.02.004.
  46. Espana P., Capelastegui A., Mar C. et al. Performance of pro-adrenomedullin for identifying adverse outcomes in community-acquired pneumonia. Journal of Infection. 2015; 70(5): 457-66. https://dx.doi.org/10.1016/j.jinf.2014.12.003.
  47. Pereira J., Azevedo A., Basilio C. et al. Mid-regional proadrenomedullin: An early marker of response in critically ill patients with severe community-acquired pneumonia? Rev Port Pneumol (2006). 2016; 22(6): 308-14. https://dx.doi.org/10.1016/j.rppnen.2016.03.012.
  48. Rudnov V., Kulabukov V. SEPSIS-3: Updated main definitions, potential problems and next practical steps. Messenger of Anesthesiology and Resuscitation. 2016; 13(4): 4-11. https://dx.doi.org/10.21292/2078-5658-2016-13-4-4-11.
  49. Bloos F., Reinhart K. Rapid diagnosis of sepsis. Virulence. 2013; 5(1): 154-60. https://dx.doi.org/10.4161/viru.27393.
  50. Elke G., Bloos F., Wilson D. et al. The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis - a secondary analysis of a large randomised controlled trial. Critical Care. 2018; 22(1): 79. https://dx.doi.org/10.1186/s13054-018-2001-5.
  51. Mebazaa A., Geven C., Hollinger A. et al. Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study. Critical Care. 2018; 22(1): 354. https://dx.doi.org/10.1186/s13054-018-2243-2
  52. Andaluz-Ojeda D., Nguyen H., Meunier-Beillard N. et al. Superior accuracy of mid-regional proadrenomedullin for mortality prediction in sepsis with varying levels of illness severity. Ann Intensive Care. 2017; 7(1): 15. https://dx.doi.org/10.1186/s13613-017-0238-9.
  53. Garcia de Guadiana-Romualdo L., Calvo Nieves M., Rodriguez Mulero M. et al. MR-proADM as marker of endotheliitis predicts COVID-19 severity. Eur J Clin Invest. 2021; 51(5): e13511. https://dx.doi.org/10.1111/eci.13511.
  54. Lo Sasso B., Gambino C., Scichilone N. et al. Clinical utility of midregional proadrenomedullin in patients with COVID-19. Lab Med. 2021; 52(5): 493-98. https://dx.doi.org/10.1093/labmed/lmab032.

Supplementary files

Supplementary Files
Action
1. JATS XML

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies