Concentration-dependent effects of dichloroacetate in type 2 diabetic hearts assessed by hyperpolarized [1-
DCA
MRI
T2DM
ZDF
heart
hyperpolarization
Journal
NMR in biomedicine
ISSN: 1099-1492
Titre abrégé: NMR Biomed
Pays: England
ID NLM: 8915233
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
14
12
2021
received:
28
07
2021
accepted:
15
12
2021
pubmed:
29
12
2021
medline:
24
5
2022
entrez:
28
12
2021
Statut:
ppublish
Résumé
Personalized medicine or individualized therapy promises a paradigm shift in healthcare. This is particularly true in complex and multifactorial diseases such as diabetes and the multitude of related pathophysiological complications. Diabetic cardiomyopathy represents an emerging condition that could be effectively treated if better diagnostic and, in particular, better therapeutic monitoring tools were available. In this study, we investigate the ability to differentiate low and high doses of metabolically targeted therapy in an obese type 2 diabetic rat model. Low-dose dichloroacetate (DCA) treatment was associated with increased lactate production, while no or little change was seen in bicarbonate production. High-dose DCA treatment was associated with a significant metabolic switch towards increased bicarbonate production. These findings support further studies using hyperpolarized [1-
Substances chimiques
Acetates
0
Bicarbonates
0
Pyruvic Acid
8558G7RUTR
Dichloroacetic Acid
9LSH52S3LQ
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e4678Informations de copyright
© 2021 John Wiley & Sons, Ltd.
Références
Jia G, Hill MA, Sowers JR. Diabetic cardiomyopathy. Circ Res. 2018;122(4):624-638.
Tan Y, Zhang Z, Zheng C, Wintergerst KA, Keller BB, Cai L. Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence. Nat Rev Cardiol. 2020;17(9):585-607.
Karwi QG, Uddin GM, Ho KL, Lopaschuk GD. Loss of metabolic flexibility in the failing heart. Front Cardiovasc Med. 2018;5:68.
Neubauer S. The failing heart-an engine out of fuel. N Engl J Med. 2007;356(11):1140-1151.
Peterzan MA, Lygate CA, Neubauer S, Rider OJ. Metabolic remodeling in hypertrophied and failing myocardium: a review. Am J Physiol Heart Circ Physiol. 2017;313(3):H597-H616.
Le Page LM, Rider OJ, Lewis AJ, et al. Increasing pyruvate dehydrogenase flux as a treatment for diabetic cardiomyopathy: a combined 13C hyperpolarized magnetic resonance and echocardiography study. Diabetes. 2015;64(8):2735-2743.
Peterson LR, Gropler RJ. Metabolic and molecular imaging of the diabetic cardiomyopathy. Circ Res. 2020;126(11):1628-1645.
Goodwin GW, Taegtmeyer H. Improved energy homeostasis of the heart in the metabolic state of exercise. Am J Physiol Heart Circ Physiol. 2000;279(4):H1490-H1501.
Kato T, Niizuma S, Inuzuka Y, et al. Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure. Circ Heart Fail. 2010;3(3):420-430.
Piao L, Fang YH, Cadete VJ, et al. The inhibition of pyruvate dehydrogenase kinase improves impaired cardiac function and electrical remodeling in two models of right ventricular hypertrophy: resuscitating the hibernating right ventricle. J Mol Med. 2010;88(1):47-60.
Gibb AA, Epstein PN, Uchida S, et al. Exercise-induced changes in glucose metabolism promote physiological cardiac growth. Circulation. 2017;136(22):2144-2157.
von Morze C, Allu PKR, Chang GY, et al. Non-invasive detection of divergent metabolic signals in insulin deficiency vs. insulin resistance in vivo. Sci Rep. 2018;8(1):2088.
Xanthopoulos A, Starling RC, Kitai T, Triposkiadis F. Heart failure and liver disease: cardiohepatic interactions. JACC: Heart Failure. 2019;7(2):87-97.
Li X, Liu J, Hu H, et al. Dichloroacetate ameliorates cardiac dysfunction caused by ischemic insults through AMPK signal pathway-not only shifts metabolism. Toxicol Sci. 2019;167(2):604-617.
Daniels A, Linz D, van Bilsen M, et al. Long-term severe diabetes only leads to mild cardiac diastolic dysfunction in Zucker diabetic fatty rats. Eur J Heart Fail. 2012;14(2):193-201.
Laustsen C, Østergaard JA, Lauritzen MH, et al. Assessment of early diabetic renal changes with hyperpolarized [1-13C]pyruvate. Diabetes Metab Res Rev. 2013;29(2):125-129.
Schroeder MA, Cochlin LE, Heather LC, Clarke K, Radda GK, Tyler DJ. In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance. Proc Natl Acad Sci. 2008;105(33):12051-12056.
Gobel FL, Norstrom LA, Nelson RR, Jorgensen CR, Wang Y. The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation. 1978;57(3):549-556.
Miller JJ, Cochlin L, Clarke K, Tyler DJ. Weighted averaging in spectroscopic studies improves statistical power. Magn Reson Med. 2017;78(6):2082-2094.
Hattori N, Tamaki N, Kudoh T, et al. Abnormality of myocardial oxidative metabolism in noninsulin-dependent diabetes mellitus. J Nucl Med. 1998;39(11):1835-1840.
Kal JE, Van Wezel HB, Vergroesen I. A critical appraisal of the rate pressure product as index of myocardial oxygen consumption for the study of metabolic coronary flow regulation. Int J Cardiol. 1999;71(2):141-148.
Bøgh N, Hansen ESS, Omann C, et al. Increasing carbohydrate oxidation improves contractile reserves and prevents hypertrophy in porcine right heart failure. Sci Rep. 2020;10(1):8158.
Wehner GJ, Jing L, Haggerty CM, et al. Routinely reported ejection fraction and mortality in clinical practice: where does the nadir of risk lie? Eur Heart J. 2020;41(12):1249-1257.
Agger P, Hyldebrandt JA, Hansen ESS, et al. Magnetic resonance hyperpolarization imaging detects early myocardial dysfunction in a porcine model of right ventricular heart failure. Eur Heart J Cardiovasc Imaging. 2020;21(1):93-101.
Lewis AJM, Miller JJ, Lau AZ, et al. Noninvasive immunometabolic cardiac inflammation imaging using hyperpolarized magnetic resonance. Circ Res. 2018;122(8):1084-1093.
Rider OJ, Apps A, Miller J, et al. Noninvasive in vivo assessment of cardiac metabolism in the healthy and diabetic human heart using hyperpolarized (13)C MRI. Circ Res. 2020;126(6):725-736.
Ardenkjaer-Larsen JH, Leach AM, Clarke N, Urbahn J, Anderson D, Skloss TW. Dynamic nuclear polarization polarizer for sterile use intent. NMR Biomed. 2011;24(8):927-932.
Janich MA, Menzel MI, Wiesinger F, et al. Effects of pyruvate dose on in vivo metabolism and quantification of hyperpolarized 13C spectra. NMR Biomed. 2012;25(1):142-151.
Wen Y, Qi H, Østergaard Mariager C, et al. Sex differences in kidney function and metabolism assessed using hyperpolarized [1-(13)C]pyruvate interleaved spectroscopy and nonspecific imaging. Tomography. 2020;6(1):5-13.
Lyons MR, Peterson LR, McGill JB, et al. Impact of sex on the heart's metabolic and functional responses to diabetic therapies. Am J Physiol Heart Circ Physiol. 2013;305(11):H1584-H1591.
Hu S, Larson PE, Vancriekinge M, et al. Rapid sequential injections of hyperpolarized [1-13C]pyruvate in vivo using a sub-kelvin, multi-sample DNP polarizer. Magn Reson Imaging. 2013;31(4):490-496.
Josan S, Park JM, Hurd R, et al. In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1-13C] and [2-13C]pyruvate. NMR Biomed. 2013;26(12):1680-1687.
Dodd MS, Ball V, Bray R, et al. In vivo mouse cardiac hyperpolarized magnetic resonance spectroscopy. J Cardiovasc Magn Reson. 2013;15(1):19.
Golman K, Petersson JS, Magnusson P, et al. Cardiac metabolism measured noninvasively by hyperpolarized 13C MRI. Magn Reson Med. 2008;59(5):1005-1013.
Oh-Ici D, Wespi P, Busch J, et al. Hyperpolarized metabolic MR imaging of acute myocardial changes and recovery after ischemia-reperfusion in a small-animal model. Radiology. 2016;278(3):742-751.
Miller JJ, Lau AZ, Teh I, et al. Robust and high resolution hyperpolarized metabolic imaging of the rat heart at 7 t with 3d spectral-spatial EPI. Magn Reson Med. 2016;75(4):1515-1524.
Menichetti L, Frijia F, Flori A, et al. Assessment of real-time myocardial uptake and enzymatic conversion of hyperpolarized [1-13C]pyruvate in pigs using slice selective magnetic resonance spectroscopy. Contrast Media Mol Imaging. 2012;7(1):85-94.
Topping GJ, Heid I, Trajkovic-Arsic M, et al. Hyperpolarized 13C spectroscopy with simple slice-and-frequency-selective excitation. Biomedicine. 2021;9(2):121.
Le Page LM, Ball DR, Ball V, et al. Simultaneous in vivo assessment of cardiac and hepatic metabolism in the diabetic rat using hyperpolarized MRS. NMR Biomed. 2016;29(12):1759-1767.
Bøgh N, Hansen ESS, Mariager CØ, Bertelsen LB, Ringgaard S, Laustsen C. Cardiac pH-Imaging With Hyperpolarized MRI. Front Cardiovasc Med. 2020;7:262.
Liu B, Clanachan AS, Schulz R, Lopaschuk GD. Cardiac efficiency is improved after ischemia by altering both the source and fate of protons. Circ Res. 1996;79(5):940-948.
Liu Q, Docherty JC, Rendell JCT, Clanachan AS, Lopaschuk GD. High levels of fatty acids delay the recoveryof intracellular pH and cardiac efficiency inpost-ischemic hearts by inhibiting glucose oxidation. J Am Coll Cardiol. 2002;39(4):718-725.
Lopaschuk GD, Verma S. Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors: a state-of-the-art review. JACC Basic Transl Sci. 2020;5(6):632-644.
Atherton HJ, Dodd MS, Heather LC, et al. Role of pyruvate dehydrogenase inhibition in the development of hypertrophy in the hyperthyroid rat heart: a combined magnetic resonance imaging and hyperpolarized magnetic resonance spectroscopy study. Circulation. 2011;123(22):2552-2561.
Michelakis ED, Gurtu V, Webster L, et al. Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients. Sci Transl Med. 2017;9(413):eaao4583.
Fernandez-Caggiano M, Kamynina A, Francois AA, et al. Mitochondrial pyruvate carrier abundance mediates pathological cardiac hypertrophy. Nat Metab. 2020;2(11):1223-1231.
Zhang Y, Taufalele PV, Cochran JD, et al. Mitochondrial pyruvate carriers are required for myocardial stress adaptation. Nat Metab. 2020;2(11):1248-1264.