Amphiregulin is overexpressed in human cardiac tissue in hypothermia deaths; associations between the transcript and stress hormone levels in cardiac deaths.

Publisher: Informa Healthcare Country of Publication: England NLM ID: 8906388 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2060 (Electronic) Linking ISSN: 07853890 NLM ISO Abbreviation: Ann Med Subsets: MEDLINE

Publication: London : Informa Healthcare
Original Publication: Helsinki : Finnish Medical Society Duodecim, 1989-

Amphiregulin*/metabolism ; Amphiregulin*/genetics ; Hypothermia*/metabolism ; RNA, Messenger*/metabolism ; Hydrocortisone*/metabolism ; Myocardium*/metabolism; Humans ; Male ; Female ; Middle Aged ; Aged ; Biomarkers/metabolism ; Adult ; Epinephrine/metabolism ; Epinephrine/urine ; Norepinephrine/metabolism ; Norepinephrine/urine ; Aged, 80 and over ; Heart Diseases/metabolism ; Heart Diseases/mortality

Background: Amphiregulin (AREG) is a growth factor linked to cardioprotection and heart pathology during myocardial stress. Our aim was to investigate cardiac AREG expression, its potential as a postmortem hypothermia marker and its possible stress hormone dependency in different types of deaths.
Materials and Methods: Heart RNA was isolated from hypothermic, cardiac and non-cardiac deaths. Relative AREG mRNA levels and urine stress hormone concentrations were measured by qPCR and enzyme-linked immunosorbent assays from eight different death cause groups. Receiver operating characteristic curve was used to evaluate a cut-off point for AREG expression as a hypothermia marker. Regulatory elements were predicted by PROMO.
Results: The AREG mRNA levels were significantly higher in hypothermic deaths than in most cardiac and non-cardiac deaths. AREG expression indicated hypothermic deaths with nearly 70% sensitivity and specificity. However, high expression levels were also detected in non-ischaemic deaths. The highest concentrations of adrenaline and cortisol were detected in hypothermic deaths, while the highest noradrenaline concentrations associated with atherosclerotic heart disease (AHD) deaths with acute myocardial infarction and trauma deaths. There were no significant correlations between stress hormones and AREG mRNA in hypothermic and non-cardiac deaths, whereas moderate-to-high associations were detected in cardiac deaths. Putative response elements for cortisol and catecholamines were found in AREG .
Conclusions: Severe hypothermia activates cardiac AREG expression practicable as a postmortem hypothermia marker. Cortisol and catecholamines may act as transcriptional modifiers of this gene, especially in long-term ischaemic heart disease. However, the exact role of these hormones in upregulation of AREG during hypothermia remains unclear.

Int J Legal Med. 2020 Jan;134(1):159-162. (PMID: 30904931)
PLoS One. 2020 Feb 18;15(2):e0218910. (PMID: 32069307)
Free Radic Biol Med. 1994 Apr;16(4):465-76. (PMID: 8005532)
J Physiol Pharmacol. 2022 Feb;73(1):. (PMID: 35793762)
Semin Cell Dev Biol. 2014 Apr;28:31-41. (PMID: 24463227)
Nucleic Acids Res. 2003 Jul 1;31(13):3651-3. (PMID: 12824386)
J Vet Med A Physiol Pathol Clin Med. 2002 Aug;49(6):286-8. (PMID: 12227469)
Clin Exp Pharmacol Physiol. 2012 Feb;39(2):179-93. (PMID: 22066679)
J Biol Chem. 2005 Feb 4;280(5):3974-81. (PMID: 15509566)
Medicine (Baltimore). 2020 Feb;99(9):e19399. (PMID: 32118793)
PLoS One. 2015 May 21;10(5):e0127854. (PMID: 25996932)
Ann Endocrinol (Paris). 2021 Jun;82(3-4):193-197. (PMID: 32473788)
Biol Direct. 2022 Aug 22;17(1):21. (PMID: 35996142)
J Forensic Sci. 2011 Sep;56(5):1213-8. (PMID: 21595691)
Proc Natl Acad Sci U S A. 1988 Sep;85(17):6528-32. (PMID: 3413110)
Am J Forensic Med Pathol. 1991 Dec;12(4):300-5. (PMID: 1807139)
Endocrinology. 2004 Nov;145(11):5177-84. (PMID: 15284208)
Circ Res. 2023 Mar 17;132(6):690-703. (PMID: 36779349)
J Biol Chem. 1993 Feb 5;268(4):2924-31. (PMID: 7679104)
Nat Med. 2017 May;23(5):611-622. (PMID: 28394333)
Circulation. 2004 Sep 14;110(11 Suppl 1):II280-6. (PMID: 15364876)
FEBS Lett. 2012 Sep 21;586(19):3500-2. (PMID: 22967896)
Bioinformatics. 2002 Feb;18(2):333-4. (PMID: 11847087)
FASEB J. 2020 Feb;34(2):2882-2895. (PMID: 31908022)
Sci Rep. 2020 Sep 22;10(1):15432. (PMID: 32963265)
Cells. 2023 May 11;12(10):. (PMID: 37408201)
Ther Hypothermia Temp Manag. 2013 Jun;3(2):63-73. (PMID: 23781398)
Hum Reprod. 2010 Oct;25(10):2569-78. (PMID: 20719813)
Int J Legal Med. 2019 Mar;133(2):335-345. (PMID: 29959558)
J Forensic Leg Med. 2023 May;96:102516. (PMID: 37011448)
Front Cell Dev Biol. 2021 Dec 13;9:732952. (PMID: 34966735)
JAMA. 2013 Nov 27;310(20):2191-4. (PMID: 24141714)
Anesthesiology. 2020 Apr;132(4):763-780. (PMID: 31794514)
Exp Cell Res. 2020 May 15;390(2):111950. (PMID: 32188578)
Int J Legal Med. 2012 Sep;126(5):747-56. (PMID: 22752749)
Development. 1999 Jun;126(12):2739-50. (PMID: 10331984)
Nat Commun. 2018 Feb 26;9(1):816. (PMID: 29483579)
Methods. 2001 Dec;25(4):402-8. (PMID: 11846609)
Int J Legal Med. 2013 Mar;127(2):267-76. (PMID: 22773274)

Keywords: Amphiregulin; cardiac stress; catecholamines; cortisol; hypothermia and cardiovascular deaths; ischaemia; postmortem hypothermia marker
Local Abstract: [plain-language-summary] Amphiregulin appears to play a role in both protective and harmful cardiac events during acute cold stress and chronic ischaemic stress, respectively.Adrenaline, noradrenaline and cortisol can act as transcriptional regulators of amphiregulin, particularly during oxidative stress associated with AHD.High level of cardiac amphiregulin mRNA seems to be a sign of antemortem hypothermia.

0 (Amphiregulin)
0 (RNA, Messenger)
WI4X0X7BPJ (Hydrocortisone)
0 (Biomarkers)
YKH834O4BH (Epinephrine)
X4W3ENH1CV (Norepinephrine)
0 (AREG protein, human)

Date Created: 20241107 Date Completed: 20241107 Latest Revision: 20241112

20241113

PMC11544741

10.1080/07853890.2024.2420862

39506618