Plasma Amino Acid Abnormalities in Chronic Heart Failure. Mechanisms, Potential Risks and Targets in Human Myocardium Metabolism

Roberto Aquilani, Maria Teresa La Rovere, Daniela Corbellini, Evasio Pasini, Manuela Verri, Annalisa Barbieri, Anna Maria Condino, Federica Boschi, Roberto Aquilani, Maria Teresa La Rovere, Daniela Corbellini, Evasio Pasini, Manuela Verri, Annalisa Barbieri, Anna Maria Condino, Federica Boschi

Abstract

The goal of this study was to measure arterial amino acid levels in patients with chronic heart failure (CHF), and relate them to left ventricular function and disease severity. Amino acids (AAs) play a crucial role for heart protein-energy metabolism. In heart failure, arterial AAs, which are the major determinant of AA uptake by the myocardium, are rarely measured. Forty-one subjects with clinically stable CHF (New York Heart Association (NYHA) class II to IV) were analyzed. After overnight fasting, blood samples from the radial artery were taken to measure AA concentrations. Calorie (KcalI), protein-, fat-, carbohydrate-intake, resting energy expenditure (REE), total daily energy expenditure (REE × 1.3), and cardiac right catheterization variables were all measured. Eight matched controls were compared for all measurements, with the exception of cardiac catheterization. Compared with controls, CHF patients had reduced arterial AA levels, of which both their number and reduced rates are related to Heart Failure (HF) severity. Arterial aspartic acid correlated with stroke volume index (r = 0.6263; p < 0.0001) and cardiac index (r = 0.4243; p = 0.0028). The value of arterial aspartic acid (µmol/L) multiplied by the cardiac index was associated with left ventricular ejection fraction (r = 0.3765; p = 0.0076). All NYHA groups had adequate protein intake (≥1.1 g/kg/day) and inadequate calorie intake (KcalI < REE × 1.3) was found only in class IV patients. This study showed that CHF patients had reduced arterial AA levels directly related to clinical disease severity and left ventricular dysfunction.

Keywords: CHF; NYHA classes; arterial amino acids; left ventricular function; nutritional adequacy.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Relationships between arterial aspartic acid and left ventricular (LV) function. Correlation between Aspartic acid and stroke volume index (panel A), Cardiac Index (panel B). The (panel C) shows the correlation between arterial Aspartic acid times cardiac index and left ventricular ejection fraction.
Figure 1
Figure 1
Relationships between arterial aspartic acid and left ventricular (LV) function. Correlation between Aspartic acid and stroke volume index (panel A), Cardiac Index (panel B). The (panel C) shows the correlation between arterial Aspartic acid times cardiac index and left ventricular ejection fraction.
Figure 2
Figure 2
Negative correlation between arterial Aspartic acid levels and hemodynamic parameters. Arterial Aspartic acid negatively correlates with Double Product (panel A) and body resting VO2 (panel B).
Figure 3
Figure 3
Synthesis of mechanisms for reduced arterial amino acids levels in clinically stable chronic heart failure (CHF).

References

    1. Bing R.J., Siegel A., Ungar I., Gilbert M. Metabolism of the human heart: II. Studies on fat, ketone and amino acid metabolism. Am. J. Med. 1954;16:504–515. doi: 10.1016/0002-9343(54)90365-4.
    1. Morgan H.E., Earl D.C., Broadus A., Wolpert E.B., Giger K.E., Jefferson L.S. Regulation of protein synthesis in heart muscle I. Effect of amino acid levels on protein synthesis. J. Biol. Chem. 1971;246:2152–2162.
    1. Young L.H., McNulty P.H., Morgan C., Deckelbaum L.I., Zaret B.L., Barrett E.J. Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion. J. Clin. Investig. 1991;87:554–560. doi: 10.1172/JCI115030.
    1. Martin A.F. Turnover of cardiac troponin subunits. Kinetic evidence for a precursor pool of troponin-I. J. Biol. Chem. 1981;256:964–968.
    1. Davis E.J., Bremer J. Studies with isolated surviving rat hearts. Interdependence of free amino acids and citric-acid-cycle intermediates. Eur. J. Biochem. 1973;38:86–97. doi: 10.1111/j.1432-1033.1973.tb03037.x.
    1. Burns A.H., Reddy W.J. Amino acid stimulation of oxygen and substrate utilization by cardiac myocytes. Am. J. Physiol. 1978;235:E461–E466.
    1. Rosenkranz E.R., Okamoto F., Buckberg G.D., Robertson J.M., Vinten-Johansen J., Bugyi H.I. Safety of prolonged aortic clamping with blood cardioplegia. III. Aspartate enrichment of glutamate-blood cardioplegia in energy-depleted hearts after ischemic and reperfusion injury. J. Thorac. Cardiovasc. Surg. 1986;91:428–435.
    1. Barrio J.R., Egbert J.E., Henze E., Schelbert H.R., Baumgartner F.J. L-[4-11C]aspartic acid: Enzymatic synthesis, myocardial uptake, and metabolism. J. Med. Chem. 1982;25:93–96. doi: 10.1021/jm00343a020.
    1. Neubauer S., Horn M., Cramer M., Harre K., Newell J.B., Peters W., Pabst T., Ertl G., Hahn D., Ingwall J.S., et al. Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation. 1997;96:2190–2196. doi: 10.1161/01.CIR.96.7.2190.
    1. Chua B., Siehl D.L., Morgan H.E. Effect of leucine and metabolites of branched chain amino acids on protein turnover in heart. J. Biol. Chem. 1979;254:8358–8362.
    1. Stanley W.C., Recchia F.A., Lopaschuk G.D. Myocardial substrate metabolism in the normal and failing heart. Physiol. Rev. 2005;85:1093–1129. doi: 10.1152/physrev.00006.2004.
    1. Schisler J.C., Grevengoed T.J., Pascual F., Cooper D.E., Ellis J.M., Paul D.S., Willis M.S., Patterson C., Jia W., Coleman R.A. Cardiac energy dependence on glucose increases metabolites related to glutathione and activates metabolic genes controlled by mechanistic target of rapamycin. J. Am. Heart Assoc. 2015;4 doi: 10.1161/JAHA.114.001136.
    1. Lai L., Leone T.C., Keller M.P., Martin O.J., Broman A.T., Nigro J., Kapoor K., Koves T.R., Stevens R., Ilkayeva O.R., et al. Energy metabolic reprogramming in the hypertrophied and early stage failing heart: A multisystems approach. Circ. Heart Fail. 2014;7:1022–1031. doi: 10.1161/CIRCHEARTFAILURE.114.001469.
    1. Schwartz R.G., Barret E.J., Francis C.K., Jacob R., Zaret B.L. Regulation of myocardial amino acid balance in the conscious dog. J. Clin. Investig. 1985;75:1204–1211. doi: 10.1172/JCI111817.
    1. Chess D.J., Stanley W.C. Role of diet and fuel overabundance in the development and progression of heart failure. Cardiovasc. Res. 2008;79:269–278. doi: 10.1093/cvr/cvn074.
    1. McNulty P.H., Louard R.J., Deckelbaum L.I., Zaret B.L., Young L.H. Hyperinsulinemia inhibits myocardial protein degradation in patients with cardiovascular disease and insulin resistance. Circulation. 1995;92:2151–2156. doi: 10.1161/01.CIR.92.8.2151.
    1. Aquilani R., Opasich C., Verri M., Boschi F., Febo O., Pasini E., Pastoris O. Is nutritional intake adequate in chronic heart failure patients? J. Am. Coll. Cardiol. 2003;42:1218–1223. doi: 10.1016/S0735-1097(03)00946-X.
    1. Frey N., Olson E.N. Cardiac hypertrophy: The good, the bad, and the ugly. Annu. Rev. Physiol. 2003;65:45–79. doi: 10.1146/annurev.physiol.65.092101.142243.
    1. Aquilani R., La Rovere M.T., Febo O., Baiardi P., Boschi F., Iadarola P., Viglio S., Dossena M., Bongiorno A.I., Pastoris O., et al. Lung anabolic activity in patients with chronic heart failure: Potential implications for clinical practice. Nutrition. 2012;28:1002–1007. doi: 10.1016/j.nut.2012.01.003.
    1. Pasini E., Aquilani R., Testa C., Baiardi P., Angioletti S., Boschi F., Verri M., Dioguardi F. Pathogenic gut flora in patients with chronic heart failure. JACC Heart Fail. 2016;4:220–227. doi: 10.1016/j.jchf.2015.10.009.
    1. Aquilani R., La Rovere M.T., Febo O., Boschi F., Iadarola P., Corbellini D., Viglio S., Bongiorno A.I., Pastoris O., Verri M. Preserved muscle protein metabolism in obese patients with chronic heart failure. Int. J. Cardiol. 2012;160:102–108. doi: 10.1016/j.ijcard.2011.03.032.
    1. Aquilani R., Iadarola P., Boschi F., Pistarini C., Arcidiaco P., Contardi A. Reduced plasma levels of tyrosine, precursor of brain catecholamines, and of essential amino acids in patients with severe traumatic brain injury after rehabilitation. Arch. Phys. Med. Rehabil. 2003;84:1258–1265. doi: 10.1016/S0003-9993(03)00148-5.
    1. Aquilani R., Opasich C., Gualco A., Verri M., Testa A., Pasini E., Viglio S., Iadarola P., Pastoris O., Dossena M., et al. Adequate energy-protein intake is not enough to improve nutritional and metabolic status in muscle-depleted patients with chronic heart failure. Eur. J. Heart Fail. 2008;10:1127–1135. doi: 10.1016/j.ejheart.2008.09.002.
    1. Weir J.B. New methods for calculating metabolic rate with special reference to protein metabolism. J. Physiol. 1949;109:1–9. doi: 10.1113/jphysiol.1949.sp004363.
    1. Toth M.J., Gottlieb S.S., Fisher M.L., Poehlman E.T. Daily energy requirements in heart failure patients. Metabolism. 1997;46:1294–1298. doi: 10.1016/S0026-0495(97)90233-X.
    1. Schutte R., Thijs L., Asayama K., Boggia J., Li Y., Hansen T.W., Liu Y.P., Kikuya M., Björklund-Bodegård K., Ohkubo T., et al. Double product reflects the predictive power of systolic pressure in the general population: Evidence from 9937 participants. Am. J. Hypertens. 2013;26:665–672. doi: 10.1093/ajh/hps119.
    1. Chacko A., Cummings J.H. Nitrogen losses from the human small bowel: Obligatory losses and the effect of physical form of food. Gut. 1988;29:809–815. doi: 10.1136/gut.29.6.809.
    1. Coggins M., Rosenzweig A. The fire within: Cardiac inflammatory signaling in health and disease. Circ. Res. 2012;110:116–125. doi: 10.1161/CIRCRESAHA.111.243196.
    1. Von Haehling S., Lainscak M., Springer J., Anker S.D. Cardiac cachexia: A systematic overview. Pharmacol. Ther. 2009;121:227–252. doi: 10.1016/j.pharmthera.2008.09.009.
    1. Conraads V.M., Bosmans J.M., Vrints C.J. Chronic heart failure: An example of a systemic chronic inflammatory disease resulting in cachexia. Int. J. Cardiol. 2002;85:33–49. doi: 10.1016/S0167-5273(02)00232-2.
    1. Anker S.D., Lechat P., Dargie H.J. Prevention and reversal of cachexia in patients with chronic heart failure by bisoprolol: Results from the CIBIS-II study. J. Am. Coll. Cardiol. 2003;41:156–157. doi: 10.1016/S0735-1097(03)81775-8.
    1. Plumley D.A., Austgen T.R., Salloum R.M., Souba W.W. Role of the lungs in maintaining amino acid homeostasis. JPEN J. Parenter. Enter. Nutr. 1990;14:569–573. doi: 10.1177/0148607190014006569.
    1. Taegtmeyer H., Harinstein M.E., Gheorghiade M. More than bricks and mortar: Comments on protein and amino acid metabolism in the heart. Am. J. Cardiol. 2008;101:3E–7E. doi: 10.1016/j.amjcard.2008.02.064.
    1. Kalantar-Zadeh K., Block G., Horwich T., Fonarow G.C. Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure. J. Am. Coll. Cardiol. 2004;43:1439–1444. doi: 10.1016/j.jacc.2003.11.039.
    1. Rau E.E., Shine K.I., Gervais A., Douglas A.M., Amos E.C., 3rd Enhanced mechanical recovery of anoxic and ischemic myocardium by amino acid perfusion. Am. J. Physiol. 1979;236:H873–H879.
    1. Arsenian M.A. Carnitine and its derivatives in cardiovascular disease. Prog. Cardiovasc. Dis. 1997;40:265–286. doi: 10.1016/S0033-0620(97)80037-0.
    1. Nakae I., Mitsunami K., Omura T., Yabe T., Tsutamoto T., Matsuo S., Takahashi M., Morikawa S., Inubushi T., Nakamura Y., et al. Proton magnetic resonance spectroscopy can detect creatine depletion associated with the progression of heart failure in cardiomyopathy. J. Am. Coll. Cardiol. 2003;42:1587–1593. doi: 10.1016/j.jacc.2003.05.005.
    1. Akhmedov A.T., Rybin V., Marín-García J. Mitochondrial oxidative metabolism and uncoupling proteins in the failing heart. Heart Fail. Rev. 2015;20:227–249. doi: 10.1007/s10741-014-9457-4.
    1. Hakuno D., Hamba Y., Toya T., Adachi T. Plasma amino acid profiling identifies specific amino acid associations with cardiovascular function in patients with systolic heart failure. PLoS ONE. 2015;10:e117325. doi: 10.1371/journal.pone.0117325.
    1. Grimble R.F., Jackson A.A., Persaud C., Wride M.J., Delers F., Engler R. Cysteine and glycine supplementation modulate the metabolic response to tumor necrosis factor alpha in rats fed a low protein diet. J. Nutr. 1992;122:2066–2073.
    1. Carubelli V., Castrini A.I., Lazzarini V., Gheorghiade M., Metra M., Lombardi C. Amino acids and derivatives, a new treatment of chronic heart failure? Heart Fail. Rev. 2015;20:39–51. doi: 10.1007/s10741-014-9436-9.
    1. Azuma J., Sawamura A., Awata N. Usefulness of taurine in chronic congestive heart failure and its prospective application. Jpn. Circ. J. 1992;56:95–99. doi: 10.1253/jcj.56.95.
    1. Azuma J., Sawamura A., Awata N., Ohta H., Hamaguchi T., Harada H., Takihara K., Hasegawa H., Yamagami T., Ishiyama T., et al. Therapeutic effect of taurine in congestive heart failure: A double-blind crossover trial. Clin. Cardiol. 1985;8:276–282. doi: 10.1002/clc.4960080507.
    1. Jeejeebhoy F., Keith M., Freeman M., Barr A., McCall M., Kurian R., Mazer D., Errett L. Nutritional supplementation with MyoVive repletes essential cardiac myocyte nutrients and reduces left ventricular size in patients with left ventricular dysfunction. Am. Heart J. 2002;143:1092–1100. doi: 10.1067/mhj.2002.121927.
    1. Beyranvand M.R., Khalafi M.K., Roshan V.D., Choobineh S., Parsa S.A., Piranfar M.A. Effect of taurine supplementation on exercise capacity of patients with heart failure. J. Cardiol. 2011;57:333–337. doi: 10.1016/j.jjcc.2011.01.007.
    1. Huang Y., Zhou M., Sun H., Wang Y. Branched-chain amino acid metabolism in heart disease: An epiphenomenon or a real culprit? Cardiovasc. Res. 2011;90:220–223. doi: 10.1093/cvr/cvr070.
    1. Divakaran V., Mann D.L. The emerging role of microRNAs in cardiac remodeling and heart failure. Circ. Res. 2008;103:1072–1083. doi: 10.1161/CIRCRESAHA.108.183087.
    1. El-Sayed H.L., Nassar M.F., Habib N.M., Elmasry O.A., Gomaa S.M. Structural and functional affection of the heart in protein energy malnutrition patients on admission and after nutritional recovery. Eur. J. Clin. Nutr. 2006;60:502–510. doi: 10.1038/sj.ejcn.1602344.
    1. King D., Smith M.L., Lye M. Gastro-intestinal protein loss in elderly patients with cardiac cachexia. Age Ageing. 1996;25:221–223. doi: 10.1093/ageing/25.3.221.
    1. Ruiz-Canela M., Hruby A., Clish C.B., Liang L., Martínez-González M.A., Hu F.B. Comprehensive metabolic profiling and incidence cardiovascular disease. A systematic review. J. Am. Heart Assoc. 2017;6 doi: 10.1161/JAHA.117.005705.
    1. Ghanim H., Abuaysheh S., Sia C.L., Korzeniewski K., Chaudhuri A., Fernandez-Real J.M., Dandona P. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: Implications for insulin resistance. Diabetes Care. 2009;32:2281–2287. doi: 10.2337/dc09-0979.
    1. Ghanim H., Sia C.L., Upadhyay M., Korzeniewski K., Viswanathan P., Abuaysheh S., Mohanty P., Dandona P. Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression. Am. J. Clin. Nutr. 2010;91:940–949. doi: 10.3945/ajcn.2009.28584.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera