A Focus on the Pathophysiology of Adrenomedullin Expression: Endothelitis and Organ Damage in Severe Viral and Bacterial Infections.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Adrenomedullin*/metabolism ; Bacterial Infections*/metabolism ; Bacterial Infections*/complications ; Virus Diseases*/metabolism ; Virus Diseases*/complications; Humans ; Inflammation/pathology ; Animals

Adrenomedullin (ADM) is a peptide hormone produced primarily in the adrenal glands, playing a crucial role in various physiological processes. As well as improving vascular integrity and decreasing vascular permeability, ADM acts as a vasodilator, positive inotrope, diuretic, natriuretic and bronchodilator, antagonizing angiotensin II by inhibiting aldosterone secretion. ADM also has antihypertrophic, anti-apoptotic, antifibrotic, antioxidant, angiogenic and immunoregulatory effects and antimicrobial properties. ADM expression is upregulated by hypoxia, inflammation-inducing cytokines, viral or bacterial substances, strength of shear stress, and leakage of blood vessels. These pathological conditions are established during systemic inflammation that can result from infections, surgery, trauma/accidents or burns. The ability to rapidly identify infections and the prognostic, predictive power makes it a valuable tool in severe viral and bacterial infections burdened by high incidence and mortality. This review sheds light on the pathophysiological processes that in severe viral or bacterial infections cause endothelitis up to the development of organ damage, the resulting increase in ADM levels dosed through its more stable peptide mid-regional proadrenomedullin (MR-proADM), the most significant studies that attest to its diagnostic and prognostic accuracy in highlighting the severity of viral or bacterial infections and appropriate therapeutic insights.

Int J Infect Dis. 2021 Oct;111:211-218. (PMID: 34461254)
JAMA. 2020 Apr 7;323(13):1239-1242. (PMID: 32091533)
Circulation. 2000 Dec 19;102(25):3039-45. (PMID: 11120692)
J Am Coll Cardiol. 2020 Aug 4;76(5):533-546. (PMID: 32517963)
Ann Intensive Care. 2017 Dec;7(1):15. (PMID: 28185230)
Front Med (Lausanne). 2022 Oct 26;9:929408. (PMID: 36388948)
Crit Care Med. 2021 Sep 1;49(9):1558-1566. (PMID: 33870918)
Am J Public Health. 2013 Mar;103(3):e43-51. (PMID: 23327249)
Peptides. 2006 Apr;27(4):661-6. (PMID: 16226342)
Front Pediatr. 2019 Aug 13;7:340. (PMID: 31456998)
FEMS Immunol Med Microbiol. 1999 Apr;23(4):289-93. (PMID: 10225288)
BMC Infect Dis. 2019 Jan 10;19(1):40. (PMID: 30630424)
Arch Biochem Biophys. 2024 Feb;752:109855. (PMID: 38097099)
J Travel Med. 2020 May 18;27(3):. (PMID: 32186711)
Am J Cardiol. 2021 May 15;147:129-136. (PMID: 33617816)
Biochem Biophys Res Commun. 1993 Apr 30;192(2):553-60. (PMID: 8387282)
J Clin Med. 2022 Aug 04;11(15):. (PMID: 35956159)
Circ Res. 2020 May 8;126(10):1456-1474. (PMID: 32264791)
Ann Transl Med. 2016 Sep;4(17):329. (PMID: 27713887)
J Crit Care. 2021 Dec;66:173-180. (PMID: 34340901)
Front Pharmacol. 2021 Mar 04;12:601909. (PMID: 33746749)
Nat Rev Immunol. 2021 May;21(5):319-329. (PMID: 33824483)
Cardiovasc Res. 2012 Oct 1;96(1):140-9. (PMID: 22843705)
Crit Care. 2010;14(3):R89. (PMID: 20482750)
Clin Chem. 2005 Oct;51(10):1823-9. (PMID: 16099941)
J Pers Med. 2022 Jan 10;12(1):. (PMID: 35055399)
Hypertens Res. 2003 Sep;26(9):731-6. (PMID: 14620929)
Front Med (Lausanne). 2023 Mar 24;10:1122367. (PMID: 37035317)
J Cardiol Cases. 2019 Dec 26;21(4):137-140. (PMID: 32256861)
Physiol Rev. 2018 Jan 1;98(1):505-553. (PMID: 29351514)
Hypertens Res. 2003 Feb;26 Suppl:S121-7. (PMID: 12630822)
Mol Endocrinol. 2000 Jun;14(6):848-62. (PMID: 10847587)
Cardiovasc Res. 1999 Sep;43(4):958-67. (PMID: 10615423)
Thromb Res. 2020 Dec;196:67-74. (PMID: 32853978)
Medicina (Kaunas). 2021 Oct 15;57(10):. (PMID: 34684146)
J Exp Med. 2011 Aug 1;208(8):1721-35. (PMID: 21788407)
J Pers Med. 2023 Jul 18;13(7):. (PMID: 37511766)
J Intensive Med. 2022 Jun 25;2(4):257-259. (PMID: 36788939)
Int J Mol Sci. 2023 Dec 13;24(24):. (PMID: 38139258)
BMJ Open. 2019 Feb 22;8(11):e020337. (PMID: 30798282)
Signal Transduct Target Ther. 2021 Nov 25;6(1):407. (PMID: 34824200)
Basic Res Cardiol. 2015 Mar;110(2):6. (PMID: 25600227)
JAMA Cardiol. 2020 Jul 1;5(7):811-818. (PMID: 32219356)
Am J Physiol Lung Cell Mol Physiol. 2001 Apr;280(4):L732-8. (PMID: 11238014)
Biochem Biophys Res Commun. 1994 Jun 30;201(3):1160-6. (PMID: 8024557)
Shock. 2018 Dec;50(6):648-654. (PMID: 29324627)
J Pers Med. 2023 Jul 18;13(7):. (PMID: 37511765)
Lancet. 2022 Feb 12;399(10325):629-655. (PMID: 35065702)
N Engl J Med. 2020 Apr 30;382(18):1708-1720. (PMID: 32109013)
Swiss Med Wkly. 2020 Dec 31;150:w20417. (PMID: 33382450)
J Cell Physiol. 1989 Apr;139(1):157-66. (PMID: 2540209)
Sci Transl Med. 2016 Apr 20;8(335):335ra55. (PMID: 27099174)
Elife. 2016 Jan 19;5:e11394. (PMID: 26780829)
Hypertension. 2004 Jan;43(1):109-16. (PMID: 14662648)
J Med Virol. 2020 Oct;92(10):1875-1883. (PMID: 32441789)
Lancet. 2011 Dec 3;378(9807):1917-30. (PMID: 22078723)
Antibiotics (Basel). 2023 May 18;12(5):. (PMID: 37237828)
J Cell Biol. 2013 Sep 16;202(6):901-16. (PMID: 24019534)
Circulation. 2018 Nov 13;138(20):e618-e651. (PMID: 30571511)
Thromb Haemost. 2007 Nov;98(5):944-51. (PMID: 18000597)
FEBS Lett. 1995 Aug 7;369(2-3):311-4. (PMID: 7649278)
Am J Respir Crit Care Med. 2017 Apr 1;195(7):906-911. (PMID: 27649072)
Br J Pharmacol. 1998 Apr;123(8):1645-54. (PMID: 9605572)
Nat Rev Drug Discov. 2014 Oct;13(10):741-58. (PMID: 25190187)
J Am Coll Cardiol. 2010 May 11;55(19):2062-76. (PMID: 20447528)
An Sist Sanit Navar. 1999 Sep-Dec;22(3):307-15. (PMID: 12886331)
J Biol Chem. 1998 Jul 3;273(27):16730-8. (PMID: 9642228)
Antioxidants (Basel). 2022 Mar 26;11(4):. (PMID: 35453325)
PLoS One. 2021 Feb 8;16(2):e0246771. (PMID: 33556140)
J Intensive Care. 2014 Jun 20;2(1):38. (PMID: 25908988)
Cold Spring Harb Perspect Biol. 2012 Dec 01;4(12):. (PMID: 23209152)
Mol Cell Biol. 2006 Apr;26(7):2511-8. (PMID: 16537897)
Circulation. 2001 Oct 16;104(16):1964-71. (PMID: 11602502)
Annu Rev Cell Dev Biol. 2019 Oct 6;35:591-613. (PMID: 31299172)
J Med Biochem. 2020 Sep 02;39(3):328-335. (PMID: 33269021)
Anaesthesiol Intensive Ther. 2014 Nov-Dec;46(5):361-80. (PMID: 25432556)
Nat Commun. 2020 Jul 17;11(1):3595. (PMID: 32681081)
Am J Physiol Endocrinol Metab. 2006 Jul;291(1):E9-E14. (PMID: 16760337)
Biochem Biophys Res Commun. 1994 Aug 30;203(1):719-26. (PMID: 8074727)
Science. 2020 May 1;368(6490):473-474. (PMID: 32303591)
Cureus. 2023 Sep 20;15(9):e45602. (PMID: 37868494)
Intensive Care Med. 2007 Apr;33(4):703-10. (PMID: 17318497)
Cell Mol Life Sci. 2015 Aug;72(16):3115-26. (PMID: 25953627)
Crit Care. 2016 Nov 9;20(1):363. (PMID: 27825364)
Circ Res. 2023 Apr 28;132(9):1185-1202. (PMID: 37104556)
J Med Virol. 2021 May;93(5):2820-2827. (PMID: 33200824)
Crit Care. 2010;14(1):R15. (PMID: 20144219)
Eur J Pharmacol. 1999 Oct 1;382(1):1-9. (PMID: 10556498)
Hypertens Res. 2003 Feb;26 Suppl:S55-9. (PMID: 12630812)
Eur J Heart Fail. 2017 Sep;19(9):1166-1175. (PMID: 28516504)
Microb Pathog. 2019 Dec;137:103763. (PMID: 31574301)
APMIS. 2015 Sep;123(9):740-8. (PMID: 26058482)
Circulation. 2021 Mar 9;143(10):1031-1042. (PMID: 33480806)
Crit Care Med. 2021 Jan 1;49(1):e41-e52. (PMID: 33196529)
Blood. 2005 Mar 1;105(5):1950-5. (PMID: 15374886)
Circulation. 2020 Jul 7;142(1):68-78. (PMID: 32293910)
Diseases. 2021 Jun 29;9(3):. (PMID: 34209705)
Eur J Heart Fail. 2019 Jun;21(6):732-743. (PMID: 30843353)
Biopharm Drug Dispos. 2007 Sep;28(6):315-22. (PMID: 17575559)
Am J Pathol. 2014 Nov;184(11):3069-83. (PMID: 25251058)
Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):615-9. (PMID: 11149956)
Eur J Clin Invest. 2021 May;51(5):e13511. (PMID: 33569769)
Crit Care. 2006;10(3):R96. (PMID: 16805922)
Medicine (Baltimore). 2016 Jan;95(4):e2124. (PMID: 26825876)
Crit Care. 2018 Dec 21;22(1):354. (PMID: 30583748)
Biochem Biophys Res Commun. 1995 Feb 6;207(1):25-32. (PMID: 7857273)
Crit Care. 2023 Mar 13;27(1):106. (PMID: 36915144)
Circulation. 2020 Jul 28;142(4):342-353. (PMID: 32469253)
Healthcare (Basel). 2018 Sep 03;6(3):. (PMID: 30177659)
Intensive Care Med. 2021 Nov;47(11):1284-1294. (PMID: 34605947)
Life Sci. 2000;66(10):855-72. (PMID: 10714887)
Am J Physiol. 1991 May;260(5 Pt 1):C1052-9. (PMID: 1709785)
Cells. 2022 Jun 15;11(12):. (PMID: 35741064)
Eur J Heart Fail. 2018 Feb;20(2):268-277. (PMID: 28960777)
Cell. 2003 Oct 17;115(2):139-50. (PMID: 14567912)
Peptides. 2001 Dec;22(12):2099-103. (PMID: 11786196)
J Clin Invest. 2019 Jun 17;129(7):2775-2791. (PMID: 31205027)
Ann Emerg Med. 2009 Mar;53(3):358-65. (PMID: 18534715)
BMC Endocr Disord. 2010 Apr 22;10:7. (PMID: 20412573)
PLoS One. 2022 Jan 6;17(1):e0262330. (PMID: 34990470)
Biomedicines. 2022 Feb 24;10(3):. (PMID: 35327335)
Am J Physiol Regul Integr Comp Physiol. 2000 Feb;278(2):R513-9. (PMID: 10666155)
Influenza Other Respir Viruses. 2009 Jan;3(1):37-49. (PMID: 19453440)
Endocrinology. 1994 Dec;135(6):2454-8. (PMID: 7988431)
Eur Heart J Acute Cardiovasc Care. 2023 Jun 2;12(6):364-371. (PMID: 36943296)
Front Med (Lausanne). 2023 Jul 11;10:1238804. (PMID: 37502361)
Minerva Anestesiol. 2019 Apr;85(4):366-375. (PMID: 30207133)
Blood. 2003 May 15;101(10):3765-77. (PMID: 12543869)
Diabetes Obes Metab. 2018 Feb;20 Suppl 1:34-46. (PMID: 29364584)
Front Med (Lausanne). 2021 Nov 30;8:680244. (PMID: 34917627)
JAMA. 2019 May 28;321(20):2003-2017. (PMID: 31104070)
Crit Care Med. 2002 May;30(5 Suppl):S207-13. (PMID: 12004237)
Neurosci Lett. 2001 Jan 19;297(3):167-70. (PMID: 11137754)
JAMA Cardiol. 2020 Jul 1;5(7):802-810. (PMID: 32211816)
Biochem Soc Trans. 2002 Aug;30(4):432-7. (PMID: 12196109)
Sci Rep. 2020 Oct 6;10(1):16605. (PMID: 33024218)
Lancet Infect Dis. 2012 Jan;12(1):36-44. (PMID: 22032844)
Peptides. 2011 Jul;32(7):1540-50. (PMID: 21645567)
J Clin Invest. 2016 Sep 1;126(9):3495-510. (PMID: 27548530)
Medicina (Kaunas). 2020 Oct 10;56(10):. (PMID: 33050538)
Ann Intensive Care. 2020 Jan 15;10(1):7. (PMID: 31940096)
Endocr Rev. 2000 Apr;21(2):138-67. (PMID: 10782362)
Front Cardiovasc Med. 2021 Jan 28;7:626975. (PMID: 33585586)
Ann Intensive Care. 2016 Dec;6(1):116. (PMID: 27878573)
Clin Infect Dis. 2005 Feb 1;40(3):415-22. (PMID: 15668866)
Biochem J. 1996 Aug 15;318 ( Pt 1):241-5. (PMID: 8761478)
J Clin Invest. 2008 Jan;118(1):29-39. (PMID: 18097473)
Crit Care Med. 2008 May;36(5):1637-40. (PMID: 18434892)
FEBS Lett. 2000 Jan 21;466(1):155-9. (PMID: 10648832)
Sci Rep. 2021 Mar 4;11(1):5121. (PMID: 33664308)
Circ Res. 2001 Jul 6;89(1):63-70. (PMID: 11440979)
Ups J Med Sci. 2023 May 03;128:. (PMID: 37223634)
Arterioscler Thromb Vasc Biol. 2019 Jun;39(6):1240-1252. (PMID: 30943772)
Crit Care. 2009;13(3):R64. (PMID: 19416526)
Am J Respir Crit Care Med. 1999 Jul;160(1):132-6. (PMID: 10390390)
Circulation. 2003 Jun 17;107(23 Suppl 1):I9-16. (PMID: 12814980)
Am J Respir Crit Care Med. 2022 Aug 15;206(4):488-500. (PMID: 35699655)
Exp Physiol. 2001 Sep;86(5):543-5. (PMID: 11571480)
Virchows Arch. 1996 Feb;427(5):461-76. (PMID: 8624575)
Front Cell Infect Microbiol. 2020 Jun 05;10:317. (PMID: 32582574)
Biochem Biophys Res Commun. 1994 Aug 30;203(1):631-9. (PMID: 8074714)
Radiology. 2023 Sep;308(3):e230743. (PMID: 37724969)
Cardiovasc Ther. 2019 Feb 5;2019:9546931. (PMID: 31772621)
Clin Res Cardiol. 2021 Jul;110(7):1029-1040. (PMID: 33211155)
Crit Care. 2020 Jul 9;24(1):411. (PMID: 32646523)
Enferm Infecc Microbiol Clin. 2014 Mar;32(3):177-90. (PMID: 23490142)
Recent Pat Endocr Metab Immune Drug Discov. 2012 Jan;6(1):4-17. (PMID: 22216776)
Trends Mol Med. 2021 Apr;27(4):314-331. (PMID: 33309601)
Eur Heart J. 2020 Oct 14;41(39):3827-3835. (PMID: 32968776)
Clin Chem. 2009 Sep;55(9):1672-9. (PMID: 19574469)
FEBS Lett. 1998 Apr 17;426(2):233-7. (PMID: 9599015)
Eur J Clin Microbiol Infect Dis. 2016 Jun;35(6):893-7. (PMID: 26936615)
Crit Care Med. 2008 Jun;36(6):1701-6. (PMID: 18496368)
Peptides. 2019 Jan;111:47-54. (PMID: 29577955)
Endocrinology. 1998 Mar;139(3):838-46. (PMID: 9492011)
Intensive Care Med Exp. 2015 Dec;3(1):44. (PMID: 26215809)
Circulation. 2000 May 16;101(19):2309-16. (PMID: 10811600)
Sci Rep. 2016 Jun 30;6:29003. (PMID: 27357373)
Emergencias. 2019 Jun;31(3):180-184. (PMID: 31210450)
J Mol Cell Cardiol. 2014 Dec;77:73-85. (PMID: 25264174)
BMC Infect Dis. 2021 Jan 7;21(1):23. (PMID: 33413127)
Dev Biol. 2005 Nov 15;287(2):301-13. (PMID: 16225857)
Crit Care. 2015 Oct 29;19:377. (PMID: 26511878)
Int J Cardiol. 2008 Nov 28;130(3):304-9. (PMID: 18625525)
Br J Clin Pharmacol. 2020 May;86(5):979-990. (PMID: 31912513)
Front Med (Lausanne). 2022 Dec 01;9:1058235. (PMID: 36530868)
BMJ Open. 2019 Jan 17;9(1):e024636. (PMID: 30782737)
Hypertension. 1998 Jan;31(1 Pt 2):505-10. (PMID: 9453353)
Medicine (Baltimore). 2018 Jan;97(3):e9496. (PMID: 29504973)
Shock. 2016 Mar;45(3):259-70. (PMID: 26871664)
Crit Care Med. 2005 Apr;33(4):819-26. (PMID: 15818111)
Biochem Biophys Res Commun. 1993 Jul 30;194(2):720-5. (PMID: 7688224)
Circ Res. 2019 Jan 4;124(1):101-113. (PMID: 30582443)
Med Princ Pract. 2018;27(3):278-284. (PMID: 29514145)
PLoS One. 2018 Aug 13;13(8):e0201491. (PMID: 30102716)
Biochem Biophys Res Commun. 1995 Oct 13;215(2):531-7. (PMID: 7487988)
Front Microbiol. 2022 Apr 07;13:797932. (PMID: 35464939)
Mayo Clin Proc. 2012 Jul;87(7):620-8. (PMID: 22683055)
PLoS Pathog. 2018 Aug 13;14(8):e1007236. (PMID: 30102747)
Int J Cardiol Heart Vasc. 2019 Mar 09;22:174-176. (PMID: 30906846)
J Trauma Acute Care Surg. 2012 Jan;72(1):293-6. (PMID: 22310138)
Biomedicines. 2023 Jul 30;11(8):. (PMID: 37626646)
Blood. 2004 Jun 1;103(11):4150-6. (PMID: 14976056)
Eur J Clin Invest. 2020 Jun;50(6):e13246. (PMID: 32307701)
Endocrinology. 1995 May;136(5):2127-34. (PMID: 7720662)
Biomedicines. 2021 Aug 23;9(8):. (PMID: 34440272)
Brain Res Mol Brain Res. 2000 Sep 30;81(1-2):1-6. (PMID: 11000473)
J Clin Invest. 2008 Jan;118(1):40-50. (PMID: 18097475)
Hypertens Res. 2022 Mar;45(3):389-400. (PMID: 34992239)
Ann Intensive Care. 2011 Apr 13;1(1):6. (PMID: 21906334)
N Engl J Med. 2020 May 21;382(21):2012-2022. (PMID: 32227758)
Ann Clin Transl Neurol. 2019 Sep;6(9):1882-1887. (PMID: 31365180)
Endocrinology. 2005 Jun;146(6):2699-708. (PMID: 15761041)
Jpn J Pharmacol. 1995 Mar;67(3):259-62. (PMID: 7630044)
Circulation. 2004 Apr 13;109(14):1789-94. (PMID: 14967720)
Peptides. 2016 Feb;76:1-13. (PMID: 26743504)
J Leukoc Biol. 2018 Apr;103(4):749-759. (PMID: 29360169)
Lancet. 2020 Nov 14;396(10262):1595-1606. (PMID: 33065034)
Crit Care Clin. 2011 Apr;27(2):407-19. (PMID: 21440209)
Curr Opin Immunol. 2003 Feb;15(1):112-9. (PMID: 12495742)
J Clin Endocrinol Metab. 1996 Apr;81(4):1449-53. (PMID: 8636349)
J Pharm Pharmacol. 2014 Dec;66(12):1734-46. (PMID: 25117796)
Am J Respir Crit Care Med. 2016 Feb 1;193(3):259-72. (PMID: 26414292)
Annu Rev Pathol. 2016 May 23;11:251-81. (PMID: 26907525)
Front Immunol. 2018 Feb 19;9:292. (PMID: 29520277)
Crit Care. 2014 Jun 16;18(3):152. (PMID: 25041977)
Cell Physiol Biochem. 2010;26(3):383-94. (PMID: 20798523)
Circulation. 1996 Nov 15;94(10):2560-5. (PMID: 8921801)
Clin Chem Lab Med. 2021 Jan 14;59(6):1165-1176. (PMID: 33554514)
Cell Mol Life Sci. 2015 Aug;72(15):2779-92. (PMID: 26091747)
J Infect. 2018 Mar;76(3):249-257. (PMID: 29246637)
Eur J Heart Fail. 2019 Feb;21(2):163-171. (PMID: 30592365)
Circulation. 2002 Jan 1;105(1):106-11. (PMID: 11772884)
Biomark Med. 2020 May;14(7):549-562. (PMID: 32462910)
Aging Dis. 2020 Jul 23;11(4):763-769. (PMID: 32765943)
Microsc Res Tech. 2002 Apr 1;57(1):3-13. (PMID: 11921351)
Biomolecules. 2020 Aug 11;10(8):. (PMID: 32796765)
J Clin Med. 2023 Aug 09;12(16):. (PMID: 37629236)
Crit Care. 2020 Jul 2;24(1):389. (PMID: 32616077)

PRIN-2017ATZ2YK This research was funded by the Ministry of Education, Universities and Research -PRIN-2017ATZ2YK. We acknowledge co-funding from Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE8 - Project Age-It: "Ageing Wel

Keywords: adrenomedullin (ADM); biomarkers; endothelitis; mid-regional proadrenomedullin (MR-proADM); sepsis; viral infection

148498-78-6 (Adrenomedullin)

Date Created: 20240619 Date Completed: 20240619 Latest Revision: 20240625

20240625

PMC11172186

10.3390/cells13110892

38891025