{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:58:54Z","timestamp":1767941934768,"version":"3.49.0"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch Heart foundation","award":["2019T041"],"award-info":[{"award-number":["2019T041"]}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004410","name":"TUBITAK","doi-asserted-by":"publisher","award":["2219 2016\/1 1059B191600332"],"award-info":[{"award-number":["2219 2016\/1 1059B191600332"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiac hypertrophy is an important risk factor for heart failure and is often accompanied by contractile dysfunction. While hypertrophic growth contributes to disease progression, the underlying molecular mechanisms remain incompletely understood. A proposed contributor is a metabolic shift toward glucose uptake, suggesting that kinases regulating this process, such as protein kinase D1 (PKD1) and downstream target phosphatidylinositol 4-kinase III\u03b2 (PI4KIII\u03b2), might be effective targets to mitigate cardiac hypertrophy-induced contractile dysfunction. We investigated whether PI4KIII\u03b2 inhibition downregulates enhanced glucose uptake in hypertrophic cardiomyocytes and thereby treats cardiac hypertrophy-induced contractile dysfunction. Hypertrophy was induced in cultured adult rat cardiomyocytes and human stem cell-derived cardiomyocytes using either phenylephrine (PE) or adenoviral PKD1 overexpression. PE-induced hypertrophy was associated with increased mRNA expression of BNP, activation of hypertrophic signaling, morphological alterations, enhanced protein synthesis and glucose uptake, and impaired contractile function. Treatment with the PI4KIII\u03b2 inhibitor MI14 prevented and reversed PE-stimulated glucose uptake and contractile dysfunction, while hypertrophic signaling, cell size, and protein synthesis remained unaffected. Similar effects on glucose uptake were observed in the PKD1 overexpression model. These findings suggest that targeting myocardial substrate metabolism via the PI4KIII\u03b2 pathway, rather than hypertrophic growth itself, could be a promising strategy to treat hypertrophy-induced contractile dysfunction.<\/jats:p>","DOI":"10.3390\/ijms27020595","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T09:34:12Z","timestamp":1767778452000},"page":"595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phosphatidylinositol 4-Kinase III\u03b2: A Therapeutic Target for Contractile Dysfunction in Hypertrophic Cardiomyocytes"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6470-722X","authenticated-orcid":false,"given":"Myrthe M. A.","family":"Willemars","sequence":"first","affiliation":[{"name":"Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Cardiovascular Research Institute Maastricht (CARIM), 6229 ER Maastricht, The Netherlands"},{"name":"Department of Physiology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8977-7198","authenticated-orcid":false,"given":"Aomin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China"},{"name":"Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Institute of Life Sciences, School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozlenen","family":"Simsek Papur","sequence":"additional","affiliation":[{"name":"Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Molecular Medicine, Institute of Health Science, Dokuz Eylul University, 35210 Izmir, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Brouns-Strzelecka","sequence":"additional","affiliation":[{"name":"Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Cardiovascular Research Institute Maastricht (CARIM), 6229 ER Maastricht, The Netherlands"},{"name":"Department of Cardiology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rick","family":"van Leeuwen","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Maastricht (CARIM), 6229 ER Maastricht, The Netherlands"},{"name":"Department of Cardiology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabina J. V.","family":"Vanherle","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5576-2406","authenticated-orcid":false,"given":"Dimitrios","family":"Kapsokalyvas","sequence":"additional","affiliation":[{"name":"Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Interdisciplinary Center for Clinical Research (IZKF), University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6533-9548","authenticated-orcid":false,"given":"Jan F. C.","family":"Glatz","sequence":"additional","affiliation":[{"name":"Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Clinical Genetics, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4316-684X","authenticated-orcid":false,"given":"Dietbert","family":"Neumann","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Maastricht (CARIM), 6229 ER Maastricht, The Netherlands"},{"name":"Department of Pathology, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5691-1634","authenticated-orcid":false,"given":"Miranda","family":"Nabben","sequence":"additional","affiliation":[{"name":"Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Cardiovascular Research Institute Maastricht (CARIM), 6229 ER Maastricht, The Netherlands"},{"name":"Department of Cardiology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Clinical Genetics, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joost J. F. P.","family":"Luiken","sequence":"additional","affiliation":[{"name":"Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Cardiovascular Research Institute Maastricht (CARIM), 6229 ER Maastricht, The Netherlands"},{"name":"Department of Cardiology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Clinical Genetics, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1016\/j.jacc.2012.08.962","article-title":"Our time: A call to save preventable death from cardiovascular disease (heart disease and stroke)","volume":"60","author":"Smith","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/S0140-6736(06)68074-4","article-title":"Controversies in ventricular remodelling","volume":"367","author":"Opie","year":"2006","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1152\/physiol.00043.2010","article-title":"The athlete\u2019s heart vs. the failing heart: Can signaling explain the two distinct outcomes?","volume":"26","author":"Weeks","year":"2011","journal-title":"Physiology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev.physiol.65.092101.142243","article-title":"Cardiac hypertrophy: The good, the bad, and the ugly","volume":"65","author":"Frey","year":"2003","journal-title":"Annu. Rev. Physiol."},{"key":"ref_5","first-page":"244","article-title":"Myocardial Protein Synthesis in Cardiac Hypertrophy","volume":"63","author":"Gudbjarnason","year":"1964","journal-title":"J. Lab. Clin. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e010926","DOI":"10.1161\/JAHA.118.010926","article-title":"Metabolic Changes in Spontaneously Hypertensive Rat Hearts Precede Cardiac Dysfunction and Left Ventricular Hypertrophy","volume":"8","author":"Li","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1159\/000369782","article-title":"Remodeling of glucose metabolism precedes pressure overload-induced left ventricular hypertrophy: Review of a hypothesis","volume":"130","author":"Kundu","year":"2015","journal-title":"Cardiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1159\/000441276","article-title":"Noninvasive Detection of Early Metabolic Left Ventricular Remodeling in Systemic Hypertension","volume":"133","author":"Hamirani","year":"2016","journal-title":"Cardiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1161\/CIRCRESAHA.118.312017","article-title":"Metabolic Coordination of Physiological and Pathological Cardiac Remodeling","volume":"123","author":"Gibb","year":"2018","journal-title":"Circ. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1161\/CIRCRESAHA.107.168211","article-title":"Protein kinase d in the cardiovascular system: Emerging roles in health and disease","volume":"102","author":"Avkiran","year":"2008","journal-title":"Circ. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119748","DOI":"10.1016\/j.bbamcr.2024.119748","article-title":"Protein kinase-D1 and downstream signaling mechanisms involved in GLUT4 translocation in cardiac muscle","volume":"1871","author":"Glatz","year":"2024","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8374","DOI":"10.1128\/MCB.24.19.8374-8385.2004","article-title":"Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5","volume":"24","author":"Vega","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"276","DOI":"10.7150\/ijbs.17617","article-title":"PKD knockdown inhibits pressure overload-induced cardiac hypertrophy by promoting autophagy via AKT\/mTOR pathway","volume":"13","author":"Zhao","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.febslet.2009.12.014","article-title":"A novel kinase inhibitor establishes a predominant role for protein kinase D as a cardiac class IIa histone deacetylase kinase","volume":"584","author":"Monovich","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5871","DOI":"10.1074\/jbc.M111.281881","article-title":"Protein kinase D1 is essential for contraction-induced glucose uptake but is not involved in fatty acid uptake into cardiomyocytes","volume":"287","author":"Dirkx","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.yjmcc.2014.08.017","article-title":"Protein kinase-D1 overexpression prevents lipid-induced cardiac insulin resistance","volume":"76","author":"Dirkx","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1007\/s00018-020-03669-7","article-title":"Phosphatidylinositol 4-kinase III\u03b2 mediates contraction-induced GLUT4 translocation and shows its anti-diabetic action in cardiomyocytes","volume":"78","author":"Sun","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Geraets, I.M.E., Coumans, W.A., Strzelecka, A., Schonleitner, P., Antoons, G., Schianchi, F., Willemars, M.M.A., Kapsokalyvas, D., Glatz, J.F.C., and Luiken, J. (2021). Metabolic Interventions to Prevent Hypertrophy-Induced Alterations in Contractile Properties In Vitro. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073620"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1161\/CIRCRESAHA.119.315483","article-title":"Metabolic Remodeling Promotes Cardiac Hypertrophy by Directing Glucose to Aspartate Biosynthesis","volume":"126","author":"Ritterhoff","year":"2020","journal-title":"Circ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ejphar.2014.11.012","article-title":"Polydatin prevents hypertrophy in phenylephrine induced neonatal mouse cardiomyocytes and pressure-overload mouse models","volume":"746","author":"Dong","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1042\/bj2660727","article-title":"Effects of catecholamines on protein synthesis in cardiac myocytes and perfused hearts isolated from adult rats. Stimulation of translation is mediated through the \u03b11-adrenoceptor","volume":"266","author":"Fuller","year":"1990","journal-title":"Biochem. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1042\/BJ20041888","article-title":"Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2)","volume":"388","author":"Rolfe","year":"2005","journal-title":"Biochem. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1172\/JCI24178","article-title":"Protein kinase cascades in the regulation of cardiac hypertrophy","volume":"115","author":"Dorn","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8862","DOI":"10.1128\/MCB.23.23.8862-8877.2003","article-title":"mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF","volume":"23","author":"Hannan","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1161\/01.RES.84.6.633","article-title":"Signaling in myocardial hypertrophy: Life after calcineurin?","volume":"84","author":"Sugden","year":"1999","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1161\/CIRCHEARTFAILURE.112.966705","article-title":"Agonist-induced hypertrophy and diastolic dysfunction are associated with selective reduction in glucose oxidation: A metabolic contribution to heart failure with normal ejection fraction","volume":"5","author":"Mori","year":"2012","journal-title":"Circ. Heart Fail."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1042\/bj3210629","article-title":"Glucose transport and glucose transporter GLUT4 are regulated by product(s) of intermediary metabolism in cardiomyocytes","volume":"321","author":"Fischer","year":"1997","journal-title":"Biochem. J."},{"key":"ref_28","first-page":"1530","article-title":"Comparison of 1-(11)C-glucose and (18)F-FDG for quantifying myocardial glucose use with PET","volume":"43","author":"Herrero","year":"2002","journal-title":"J. Nucl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.niox.2014.12.007","article-title":"Hydrogen sulfide improves glucose metabolism and prevents hypertrophy in cardiomyocytes","volume":"46","author":"Liang","year":"2015","journal-title":"Nitric Oxide"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1042\/BJ20101390","article-title":"Responses of hypertrophied myocytes to reactive species: Implications for glycolysis and electrophile metabolism","volume":"435","author":"Sansbury","year":"2011","journal-title":"Biochem. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"H1719","DOI":"10.1152\/ajpheart.00937.2009","article-title":"AFos inhibits phenylephrine-mediated contractile dysfunction by altering phospholamban phosphorylation","volume":"298","author":"Jeong","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1021\/acs.jmedchem.5b00499","article-title":"Highly Selective Phosphatidylinositol 4-Kinase III\u03b2 Inhibitors and Structural Insight into Their Mode of Action","volume":"58","author":"Mejdrova","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, S., Wong, L.Y., Neumann, D., Liu, Y., Sun, A., Antoons, G., Strzelecka, A., Glatz, J.F.C., Nabben, M., and Luiken, J. (2020). Augmenting Vacuolar H+-ATPase Function Prevents Cardiomyocytes from Lipid-Overload Induced Dysfunction. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041520"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.cardiores.2005.08.010","article-title":"Role of phospholamban phosphorylation on Thr17 in cardiac physiological and pathological conditions","volume":"68","author":"Mattiazzi","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4054","DOI":"10.1021\/pr200258m","article-title":"Top-down quantitative proteomics identified phosphorylation of cardiac troponin I as a candidate biomarker for chronic heart failure","volume":"10","author":"Zhang","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.pharmthera.2010.04.005","article-title":"Molecular distinction between physiological and pathological cardiac hypertrophy: Experimental findings and therapeutic strategies","volume":"128","author":"Bernardo","year":"2010","journal-title":"Pharmacol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1161\/01.CIR.92.5.1274","article-title":"Effect of left ventricular hypertrophy secondary to chronic pressure overload on transmural myocardial 2-deoxyglucose uptake. A 31P NMR spectroscopic study","volume":"92","author":"Zhang","year":"1995","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1161\/hc4001.097183","article-title":"Increased adenosine monophosphate-activated protein kinase activity in rat hearts with pressure-overload hypertrophy","volume":"104","author":"Tian","year":"2001","journal-title":"Circulation"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1161\/01.CIR.81.4.1353","article-title":"Effects of long-term pressure overload on regional myocardial glucose and free fatty acid uptake in rats. A quantitative autoradiographic study","volume":"81","author":"Kagaya","year":"1990","journal-title":"Circulation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1161\/01.HYP.0000144292.69599.0c","article-title":"Mechanisms for increased glycolysis in the hypertrophied rat heart","volume":"44","author":"Nascimben","year":"2004","journal-title":"Hypertension"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/ijhas.IJHAS_104_17","article-title":"Molecular mediators, characterization of signaling pathways with descriptions of cellular distinctions in pathophysiology of cardiac hypertrophy and molecular changes underlying a transition to heart failure","volume":"8","author":"Melaku","year":"2019","journal-title":"Int. J. Health Allied Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jsb.2017.08.006","article-title":"Structural analysis of phosphatidylinositol 4-kinase III\u03b2 (PI4KB)-14-3-3 protein complex reveals internal flexibility and explains 14-3-3 mediated protection from degradation in vitro","volume":"200","author":"Chalupska","year":"2017","journal-title":"J. Struct. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1749-6632.2009.05100.x","article-title":"Return to the fetal gene program: A suggested metabolic link to gene expression in the heart","volume":"1188","author":"Taegtmeyer","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"165879","DOI":"10.1016\/j.bbadis.2020.165879","article-title":"Targeting metabolic pathways to treat cardiovascular diseases","volume":"1866","author":"Glatz","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1161\/01.HYP.0000248430.26229.0f","article-title":"Low carbohydrate\/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension","volume":"48","author":"Okere","year":"2006","journal-title":"Hypertension"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1007\/s00125-010-1832-7","article-title":"Requirement for distinct vesicle-associated membrane proteins in insulin- and AMP-activated protein kinase (AMPK)-induced translocation of GLUT4 and CD36 in cultured cardiomyocytes","volume":"53","author":"Schwenk","year":"2010","journal-title":"Diabetologia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0026-895X(25)10421-5","article-title":"Nitrobenzylthioinosine-sensitive nucleoside transport system: Mechanism of inhibition by dipyridamole","volume":"30","author":"Jarvis","year":"1986","journal-title":"Mol. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1161\/01.STR.0000179044.37760.9d","article-title":"Role of adenosine and nitric oxide on the mechanisms of action of dipyridamole","volume":"36","author":"Gamboa","year":"2005","journal-title":"Stroke"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Gallo, S., Vitacolonna, A., Bonzano, A., Comoglio, P., and Crepaldi, T. (2019). ERK: A Key Player in the Pathophysiology of Cardiac Hypertrophy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092164"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S0022-2275(20)37241-2","article-title":"Uptake and metabolism of palmitate by isolated cardiac myocytes from adult rats: Involvement of sarcolemmal proteins","volume":"38","author":"Luiken","year":"1997","journal-title":"J. Lipid Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.2337\/diabetes.51.10.3113","article-title":"Insulin stimulates long-chain fatty acid utilization by rat cardiac myocytes through cellular redistribution of FAT\/CD36","volume":"51","author":"Luiken","year":"2002","journal-title":"Diabetes"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/595\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T05:17:42Z","timestamp":1767935862000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/595"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":51,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020595"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020595","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]}}}