Higher ACE2 expression levels in epicardial cells than subcutaneous stromal cells from patients with cardiovascular disease: Diabetes and obesity as possible enhancer.

Publisher: Wiley Country of Publication: England NLM ID: 0245331 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2362 (Electronic) Linking ISSN: 00142972 NLM ISO Abbreviation: Eur J Clin Invest Subsets: MEDLINE

Publication: Oxford : Wiley
Original Publication: Berlin, New York, Springer-Verlag, on behalf of the European Society for Clinical Investigation.

ADAM17 Protein/*genetics ; Angiotensin-Converting Enzyme 2/*genetics ; Diabetes Mellitus, Type 2/*genetics ; Obesity/*genetics ; Pericardium/*metabolism ; Stromal Cells/*metabolism ; Subcutaneous Fat/*metabolism; Adipogenesis/genetics ; Adipose Tissue/cytology ; Adipose Tissue/metabolism ; Aged ; Aged, 80 and over ; COVID-19 ; Cardiac Surgical Procedures ; Coronary Artery Bypass ; Female ; Heart Valve Prosthesis Implantation ; Humans ; Hypoglycemic Agents/therapeutic use ; Insulin/therapeutic use ; Logistic Models ; Male ; Metformin/therapeutic use ; Middle Aged ; Peptidyl-Dipeptidase A ; Pericardium/cytology ; RNA, Messenger/metabolism ; Receptors, Coronavirus/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; SARS-CoV-2/metabolism ; Subcutaneous Fat/cytology ; Thiazolidinediones/therapeutic use

Aims: Obesity, diabetes and cardiovascular disease are associated with COVID-19 risk and severity. Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat.
Materials and Methods: Epicardial and subcutaneous fat biopsies were obtained from 43 patients who underwent open-heart surgery. From 36 patients, biopsies were used for RNA expression analysis by real-time PCR of ACE1, ACE2 and ADAM17. From 8 patients, stromal vascular cells were submitted to adipogenesis or used for studying the treatment effects on gene expression levels. Soluble ACE2 was determined in supernatants by ELISA.
Results: Epicardial fat biopsies expressed higher levels of ACE2 (1.53 [1.49-1.61] vs 1.51 [1.47-1.56] a.u., P < .05) and lower ADAM17 than subcutaneous fat (1.67 [1.65-1.70] vs 1.70 [1.66-1.74] a.u., P < .001). Both genes were increased in epicardial fat from patients with type 2 diabetes mellitus (T2DM) (1.62 [1.50-2.28] vs 1.52 [1.49-1.55] a.u., P = .05 for ACE2 and 1.68 [1.66-1.78] vs 1.66 [1.63-1.69] a.u., P < .05 for ADAM17). Logistic regression analysis determined that T2DM was the main associated factor with epicardial ACE2 levels (P < .01). The highest ACE2 levels were found on patients with diabetes and obesity. ACE1 and ACE2 levels were not upregulated by antidiabetic treatment (metformin, insulin or thiazolidinedione). Its cellular levels, which were higher in epicardial than in subcutaneous stromal cells (1.61 [1.55-1.63] vs 1 [1-1.34]), were not correlated with the soluble ACE2.
Conclusion: Epicardial fat cells expressed higher levels of ACE2 in comparison with subcutaneous fat cells, which is enhanced by diabetes and obesity presence in patients with cardiovascular disease. Both might be risk factors for SARS-CoV-2 infection.
(© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Eur Heart J. 2020 May 14;41(19):1804-1806. (PMID: 32293672)
JAMA. 2020 May 26;323(20):2052-2059. (PMID: 32320003)
Nature. 2003 Nov 27;426(6965):450-4. (PMID: 14647384)
Cardiovasc Res. 2018 Feb 1;114(2):336-346. (PMID: 29016744)
Med Hypotheses. 2020 Nov;144:110015. (PMID: 32592919)
ScientificWorldJournal. 2014 Jan 14;2014:603409. (PMID: 24558317)
Diabetes. 2016 Jan;65(1):85-95. (PMID: 26224885)
Circulation. 2020 Aug 18;142(7):708-710. (PMID: 32795091)
Eur Heart J. 2020 Jun 21;41(24):2334-2335. (PMID: 32464652)
Nature. 2020 Mar;579(7798):270-273. (PMID: 32015507)
Lancet. 2020 Aug 1;396(10247):320-332. (PMID: 32682491)
J Virol. 2014 Jan;88(2):1293-307. (PMID: 24227843)
Cardiovasc Res. 2020 May 1;116(6):1097-1100. (PMID: 32227090)
Obes Rev. 2020 Jun;21(6):e13034. (PMID: 32281287)
Circ Res. 2020 May 8;126(10):1456-1474. (PMID: 32264791)
J Anim Physiol Anim Nutr (Berl). 2016 Dec;100(6):1139-1148. (PMID: 26452529)
Diabetes. 2016 Jan;65(1):19-21. (PMID: 26696636)
Obesity (Silver Spring). 2020 Jul;28(7):1178-1179. (PMID: 32314871)
Immunol Lett. 2014 Nov;162(1 Pt A):159-69. (PMID: 25171914)
BMC Med. 2004 May 19;2:19. (PMID: 15151696)
Methodist Debakey Cardiovasc J. 2017 Jan-Mar;13(1):20-24. (PMID: 28413578)
Am J Physiol Regul Integr Comp Physiol. 2008 Sep;295(3):R781-8. (PMID: 18650320)
Nature. 2002 Jun 20;417(6891):822-8. (PMID: 12075344)
Int J Obes (Lond). 2020 Sep;44(9):1810-1817. (PMID: 32647360)
Am J Physiol Heart Circ Physiol. 2010 Jul;299(1):H202-9. (PMID: 20435850)
Circ Heart Fail. 2009 Sep;2(5):446-55. (PMID: 19808375)
Diabetes. 2008 Feb;57(2):340-7. (PMID: 18025412)
Eur J Clin Invest. 2009 Jul;39(7):618-25. (PMID: 19453650)
Arterioscler Thromb Vasc Biol. 2017 Feb;37(2):176-178. (PMID: 28122773)
J Cell Mol Med. 2020 Sep;24(18):10958-10969. (PMID: 32767737)
Circ Res. 2000 Sep 1;87(5):E1-9. (PMID: 10969042)
Peptides. 2005 Jul;26(7):1270-7. (PMID: 15949646)
J Cell Physiol. 2014 Nov;229(11):1722-30. (PMID: 24648294)
Am J Physiol Heart Circ Physiol. 2008 Oct;295(4):H1377-84. (PMID: 18660448)
J Mol Cell Cardiol. 2014 Jan;66:167-76. (PMID: 24332999)
Obesity (Silver Spring). 2020 Jul;28(7):1195-1199. (PMID: 32271993)
Eur J Clin Invest. 2021 May;51(5):e13463. (PMID: 33251580)
Eur Heart J. 2005 Feb;26(4):322-4. (PMID: 15671047)
Lancet Respir Med. 2020 Apr;8(4):e21. (PMID: 32171062)
Eur Heart J. 2020 Jun 21;41(24):2333. (PMID: 32464641)
J Am Coll Cardiol. 2012 Feb 21;59(8):739-47. (PMID: 22340266)
Cardiovasc Res. 2020 Aug 1;116(10):1666-1687. (PMID: 32352535)

PI19/01330 Plan Estatal de I+D+I; ISCIII-Subdirección General de Evaluación y Fomento de la Investigación el Fondo Europeo de Desarrollo Regional (FEDER); IN607B 2019/02 Consellería de Economía, Emprego e Industria; SERGAS; Health Research Institute of Santiago de Compostela (IDIS)

Keywords: ACE2; COVID-19; cardiovascular disease; epicardial fat

0 (Hypoglycemic Agents)
0 (Insulin)
0 (RNA, Messenger)
0 (Receptors, Coronavirus)
0 (Thiazolidinediones)
9100L32L2N (Metformin)
EC 3.4.15.1 (ACE protein, human)
EC 3.4.15.1 (Peptidyl-Dipeptidase A)
EC 3.4.17.23 (ACE2 protein, human)
EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
EC 3.4.24.86 (ADAM17 Protein)
EC 3.4.24.86 (ADAM17 protein, human)

Date Created: 20201130 Date Completed: 20210430 Latest Revision: 20221005

20250114

PMC7744875

10.1111/eci.13463

33251580