Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction.

Publisher: Oxford Journals Country of Publication: England NLM ID: 0077427 Publication Model: Print Cited Medium: Internet ISSN: 1755-3245 (Electronic) Linking ISSN: 00086363 NLM ISO Abbreviation: Cardiovasc Res Subsets: MEDLINE

Publication: 2008- : Oxford : Oxford Journals
Original Publication: London, British Medical Assn.

Heart Failure* ; Ventricular Dysfunction, Left*; Humans ; Mice ; Animals ; Myocardium/metabolism ; Stroke Volume ; Amino Acids, Essential/metabolism ; Diet

Aims: Heart failure with reduced ejection fraction (HFrEF) is a leading cause of mortality worldwide, requiring novel therapeutic and lifestyle interventions. Metabolic alterations and energy production deficit are hallmarks and thereby promising therapeutic targets for this complex clinical syndrome. We aim to study the molecular mechanisms and effects on cardiac function in rodents with HFrEF of a designer diet in which free essential amino acids-in specifically designed percentages-substituted for protein.
Methods and Results: Wild-type mice were subjected to transverse aortic constriction (TAC) to induce left ventricle (LV) pressure overload or sham surgery. Whole-body glucose homeostasis was studied with glucose tolerance test, while myocardial dysfunction and fibrosis were measured with echocardiogram and histological analysis. Mitochondrial bioenergetics and morphology were investigated with oxygen consumption rate measurement and electron microscopy evaluation. Circulating and cardiac non-targeted metabolite profiles were analyzed by ultrahigh performance liquid chromatography-tandem mass spectroscopy, while RNA-sequencing was used to identify signalling pathways mainly affected. The amino acid-substituted diet shows remarkable preventive and therapeutic effects. This dietary approach corrects the whole-body glucose metabolism and restores the unbalanced metabolic substrate usage-by improving mitochondrial fuel oxidation-in the failing heart. In particular, biochemical, molecular, and genetic approaches suggest that renormalization of branched-chain amino acid oxidation in cardiac tissue, which is suppressed in HFrEF, plays a relevant role. Beyond the changes of systemic metabolism, cell-autonomous processes may explain at least in part the diet's cardioprotective impact.
Conclusion: Collectively, these results suggest that manipulation of dietary amino acids, and especially essential amino acids, is a potential adjuvant therapeutic strategy to treat systolic dysfunction and HFrEF in humans.
Competing Interests: Conflict of interest: None declared.
(© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Circ Heart Fail. 2016 May;9(5):. (PMID: 27166246)
J Nutr. 2004 Jun;134(6 Suppl):1583S-1587S. (PMID: 15173434)
Front Cardiovasc Med. 2018 Jun 06;5:68. (PMID: 29928647)
Annu Rev Nutr. 1984;4:409-54. (PMID: 6380539)
Br J Nutr. 2016 Apr 14;115(7):1202-17. (PMID: 26857032)
Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8277-81. (PMID: 1832775)
Acta Cardiol. 2007 Aug;62(4):381-9. (PMID: 17824299)
Nat Rev Endocrinol. 2014 Dec;10(12):723-36. (PMID: 25287287)
J Clin Invest. 2010 May;120(5):1506-14. (PMID: 20407209)
Cardiovasc Res. 2015 May 1;106(2):249-60. (PMID: 25750189)
Cardiovasc Res. 2012 Jun 1;94(3):408-17. (PMID: 22406748)
Biochim Biophys Acta. 2016 Jul;1863(7 Pt B):1894-903. (PMID: 26775585)
Card Fail Rev. 2017 Apr;3(1):7-11. (PMID: 28785469)
ESC Heart Fail. 2021 Apr;8(2):1342-1348. (PMID: 33502122)
Biochim Biophys Acta. 2016 Dec;1862(12):2270-2275. (PMID: 27639835)
Nat Commun. 2018 Jul 26;9(1):2935. (PMID: 30050148)
Front Physiol. 2019 Sep 04;10:1140. (PMID: 31551816)
Lancet. 2019 Mar 9;393(10175):1034-1044. (PMID: 30860029)
JCI Insight. 2020 Mar 26;5(6):. (PMID: 32213702)
Br J Pharmacol. 2017 Jun;174(11):1366-1377. (PMID: 27638647)
Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7074-9. (PMID: 17438289)
J Am Heart Assoc. 2019 Jun 18;8(12):e012673. (PMID: 31185774)
Cardiovasc Res. 2010 Jan 15;85(2):376-84. (PMID: 19843514)
Nutrients. 2016 Jul 22;8(7):. (PMID: 27455314)
Nat Rev Cardiol. 2023 Feb;20(2):77-89. (PMID: 36064969)
Diabetes. 2020 Nov;69(11):2324-2339. (PMID: 32778569)
Circulation. 2016 May 24;133(21):2038-49. (PMID: 27059949)
N Engl J Med. 2007 Mar 15;356(11):1140-51. (PMID: 17360992)
Eur J Prev Cardiol. 2019 Jan;26(1):22-32. (PMID: 30196724)
Circulation. 2016 Mar 29;133(13):1249-63. (PMID: 26915633)
Cell Metab. 2007 Jul;6(1):25-37. (PMID: 17618854)
Clin Nutr. 2022 Aug;41(8):1827-1833. (PMID: 35839544)
J Clin Invest. 2009 Jun;119(6):1678-87. (PMID: 19411760)
Nature. 2019 Aug;572(7771):614-619. (PMID: 31435015)
Circ Res. 2013 Aug 30;113(6):709-24. (PMID: 23989714)
Circulation. 2019 Mar 5;139(10):e56-e528. (PMID: 30700139)
Cell Rep. 2016 Jan 12;14(2):243-54. (PMID: 26748706)
Nat Metab. 2020 Nov;2(11):1232-1247. (PMID: 33106690)
Physiol Rev. 2005 Jul;85(3):1093-129. (PMID: 15987803)
J Nutr Sci Vitaminol (Tokyo). 2019;65(5):383-389. (PMID: 31666474)
Circ Res. 2016 May 13;118(10):1659-701. (PMID: 27012580)
Genome Biol. 2004;5(10):R80. (PMID: 15461798)
Bioinformatics. 2010 Jan 1;26(1):139-40. (PMID: 19910308)
Bioinformatics. 2011 Oct 15;27(20):2917-8. (PMID: 21893519)
Cell Metab. 2009 Apr;9(4):311-26. (PMID: 19356713)
Cardiovasc Diabetol. 2019 Jul 5;18(1):86. (PMID: 31277657)
JCI Insight. 2016 Feb;2(1):. (PMID: 26998524)
Circulation. 2003 Apr 1;107(12):1664-70. (PMID: 12668503)
J Clin Invest. 2018 Aug 31;128(9):3716-3726. (PMID: 30124471)
J Card Fail. 2015 Jun;21(6):460-9. (PMID: 25911126)
Circ Heart Fail. 2013 Nov;6(6):1116-23. (PMID: 24107587)
Cell Metab. 2010 Oct 6;12(4):362-372. (PMID: 20889128)
JACC Basic Transl Sci. 2017 Jun;2(3):297-310. (PMID: 28944310)
Am J Physiol. 1972 May;222(5):1199-203. (PMID: 4259993)
Circ Res. 2019 Sep 13;125(7):707-719. (PMID: 31412728)
Eur J Heart Fail. 2016 Sep;18(9):1106-18. (PMID: 27109894)
Circ Heart Fail. 2013 Nov;6(6):1165-71. (PMID: 23985432)
Eur J Heart Fail. 2014 May;16(5):543-50. (PMID: 24574190)
N Engl J Med. 1969 Oct 9;281(15):811-6. (PMID: 5809519)
Sci Transl Med. 2016 Feb 17;8(326):326ra22. (PMID: 26888430)
Circ Heart Fail. 2014 Jul;7(4):634-42. (PMID: 24762972)
Circulation. 2004 Jun 22;109(24):3050-5. (PMID: 15184287)
J Cell Mol Med. 2016 Feb;20(2):302-12. (PMID: 26578237)
Cell Metab. 2012 May 2;15(5):764-77. (PMID: 22560225)
Heart Fail Rev. 2015 Jan;20(1):39-51. (PMID: 24925377)
Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H977-83. (PMID: 11179038)
Circulation. 2022 Mar 15;145(11):829-846. (PMID: 35235343)
J Am Heart Assoc. 2019 Jun 4;8(11):e011625. (PMID: 31433721)
Heart Vessels. 2012 Nov;27(6):576-84. (PMID: 21947607)
Diabetes. 2016 Jan;65(1):25-33. (PMID: 26696638)
Am J Epidemiol. 2013 Oct 15;178(8):1226-32. (PMID: 24008908)
Cardiovasc Res. 2013 Mar 15;97(4):676-85. (PMID: 23257023)

Keywords: Amino acids; Heart failure; Mitochondrial function; Nutrition; Transcriptomic reprogramming

0 (Amino Acids, Essential)

Date Created: 20230110 Date Completed: 20230504 Latest Revision: 20230504

20230506

PMC10153641

10.1093/cvr/cvad005

36626303