Increased acylcarnitines in infant heart failure indicate fatty acid oxidation inhibition: towards therapeutic options?

Acylcarnitines Children Dilated cardiomyopathy Fatty acid beta-oxidation Heart failure

Journal

ESC heart failure
ISSN: 2055-5822
Titre abrégé: ESC Heart Fail
Pays: England
ID NLM: 101669191

Informations de publication

Date de publication:
Oct 2023
Historique:
revised: 07 06 2023
received: 17 02 2023
accepted: 08 06 2023
pubmed: 24 8 2023
medline: 24 8 2023
entrez: 24 8 2023
Statut: ppublish

Résumé

Heart failure in adults is characterized by reduction of long-chain fatty acid oxidation in favour of carbohydrate metabolism. This adaptive phenomenon becomes maladaptive because energy conversion decreases and lipid toxic derivatives known to impair cardiac function are accumulating. No data are available concerning metabolic modification in heart failure in children. In order to evaluate the fatty acid oxidation in children suffering from heart failure, acylcarnitine profiles on dried blood spots were obtained from children under 16 years old with dilated cardiomyopathy and clinical heart failure (DCM-HF) and control children. Nine children were included in the DCM-HF group and eight in the control group. Acylcarnitine profiles revealed a significant 3.1-fold increase of total acylcarnitines (sum of C3 to C18 acylcarnitine species) in DCM-HF children compared with controls. This result persisted considering the sum of long-chain acylcarnitines (sum of C14 to C18 species), medium-chain acylcarnitines (sum of C8 to C12 species), and short-chain acylcarnitines (sum of C3 to C6 species), respectively, 2.0-, 2.6-, and 1.9-fold increase compared with the control group. A significant linear correlation was found between left ventricular dilatation or ejection fraction and acylcarnitines accumulation. Finally, acylcarnitine ratio C16OH/C16 and C18OH/C18 enhanced in the DCM-HF group, suggesting a diminution of the long-chain hydroxyl acyl-CoA dehydrogenase activity. Our results suggest down-regulation of fatty acid oxidation in children with heart failure. Such lipidomic alteration could worsen heart function and may suggest considering a metabolic treatment of heart failure in children.

Identifiants

pubmed: 37614055
doi: 10.1002/ehf2.14449
pmc: PMC10567663
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3114-3122

Informations de copyright

© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Références

Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1292-1299
pubmed: 28392417
J Pharm Biomed Anal. 2018 Jan 30;148:273-279
pubmed: 29059617
Coron Artery Dis. 1996 Feb;7(2):116-23
pubmed: 8813442
Circulation. 1996 Dec 1;94(11):2837-42
pubmed: 8941110
Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H140-8
pubmed: 16920812
J Proteome Res. 2018 Nov 2;17(11):3657-3670
pubmed: 30256116
Clin Sci (Lond). 2007 Aug;113(4):205-12
pubmed: 17319797
J Cardiovasc Pharmacol. 2000 Jul;36(1):14-21
pubmed: 10892655
Physiol Rev. 2010 Jan;90(1):207-58
pubmed: 20086077
Mol Genet Metab Rep. 2022 Jun 03;32:100884
pubmed: 35677112
Circulation. 2010 Oct 19;122(16):1562-9
pubmed: 20921440
Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1425-36
pubmed: 15550523
J Am Heart Assoc. 2016 Jul 29;5(8):
pubmed: 27473038
J Am Coll Cardiol. 2015 Apr 21;65(15):1509-20
pubmed: 25881932
J Lipid Res. 2008 Oct;49(10):2101-12
pubmed: 18515784
Am J Physiol Heart Circ Physiol. 2017 Oct 1;313(4):H768-H781
pubmed: 28710072
Nat Rev Endocrinol. 2015 Oct;11(10):617-25
pubmed: 26303601
Circulation. 1997 Oct 7;96(7):2190-6
pubmed: 9337189
J Inherit Metab Dis. 1990;13(3):321-4
pubmed: 2122093
J Am Coll Cardiol. 2016 Jan 26;67(3):291-9
pubmed: 26796394
Circ Res. 2003 Aug 8;93(3):e33-7
pubmed: 12869392
JIMD Rep. 2018;39:63-74
pubmed: 28755359
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1226-31
pubmed: 12552126
ESC Heart Fail. 2021 Apr;8(2):1472-1481
pubmed: 33547769
Mol Genet Metab. 2016 Nov;119(3):223-231
pubmed: 27590926
Cardiovasc Res. 2011 May 1;90(2):202-9
pubmed: 21289012
Ther Drug Monit. 2016 Feb;38(1):73-8
pubmed: 26309031
PLoS One. 2012;7(7):e41686
pubmed: 22848566
Circ Heart Fail. 2009 Jan;2(1):63-70
pubmed: 19808316
Biochim Biophys Acta. 2013 Apr;1833(4):857-65
pubmed: 22960640
ESC Heart Fail. 2023 Oct;10(5):3114-3122
pubmed: 37614055

Auteurs

Jean Issa (J)

Institut des Cardiopathies Congénitales de Tours, Hôpital Gatien de Clocheville, CHU Tours, 49 Boulevard Béranger, Tours, 37000, France.
Université François Rabelais, Tours, France.

Pierre Lodewyckx (P)

Institut des Cardiopathies Congénitales de Tours, Hôpital Gatien de Clocheville, CHU Tours, 49 Boulevard Béranger, Tours, 37000, France.
Université François Rabelais, Tours, France.

Hélène Blasco (H)

Université François Rabelais, Tours, France.
Service de Biochimie et Biologie Moléculaire, CHU Tours, Tours, France.

Isabelle Benz-de-Bretagne (I)

Service de Biochimie et Biologie Moléculaire, CHU Tours, Tours, France.

François Labarthe (F)

Université François Rabelais, Tours, France.
Département de Pédiatrie, CHU de Tours, Tours, France.
INSERM UMR 1069, Tours, France.

Bruno Lefort (B)

Institut des Cardiopathies Congénitales de Tours, Hôpital Gatien de Clocheville, CHU Tours, 49 Boulevard Béranger, Tours, 37000, France.
Université François Rabelais, Tours, France.
INSERM UMR 1069, Tours, France.
FHU PreciCare, Tours, France.

Classifications MeSH