{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T06:56:35Z","timestamp":1793775395264,"version":"4.6.1"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004431","name":"Fondation de France","doi-asserted-by":"publisher","award":["00107048"],"award-info":[{"award-number":["00107048"]}],"id":[{"id":"10.13039\/501100004431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR- 20-CE14-0013-01"],"award-info":[{"award-number":["ANR- 20-CE14-0013-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"name":"French Ministry of Health and Research National Program","award":["IR-27-24"],"award-info":[{"award-number":["IR-27-24"]}]},{"DOI":"10.13039\/501100005630","name":"Soci\u00e9t\u00e9 Fran\u00e7aise de Cardiologie","doi-asserted-by":"publisher","award":["Bourse C\u0153ur, Vaisseaux, Diab\u00e8te 2011"],"award-info":[{"award-number":["Bourse C\u0153ur, Vaisseaux, Diab\u00e8te 2011"]}],"id":[{"id":"10.13039\/501100005630","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Diabetol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Type 2 diabetes (T2D) is a frequent comorbidity encountered in patients with severe aortic stenosis (AS), leading to an adverse left ventricular (LV) remodeling and dysfunction. Metabolic alterations have been suggested as contributors of the deleterious effect of T2D on LV remodeling and function in patients with severe AS, but so far, the underlying mechanisms remain unclear. Mitochondria play a central role in the regulation of cardiac energy metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We aimed to explore the mitochondrial alterations associated with the deleterious effect of T2D on LV remodeling and function in patients with AS, preserved ejection fraction, and no additional heart disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We combined an in-depth clinical, biological and echocardiography phenotype of patients with severe AS, with (n\u2009=\u200934) or without (n\u2009=\u200950) T2D, referred for a valve replacement, with transcriptomic and histological analyses of an intra-operative myocardial LV biopsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      T2D patients had similar AS severity but displayed worse cardiac remodeling, systolic and diastolic function than non-diabetics. RNAseq analysis identified 1029 significantly differentially expressed genes. Functional enrichment analysis revealed several T2D-specific upregulated pathways despite comorbidity adjustment, gathering regulation of inflammation, extracellular matrix organization, endothelial function\/angiogenesis, and adaptation to cardiac hypertrophy. Downregulated gene sets independently associated with T2D were related to mitochondrial respiratory chain organization\/function and mitochondrial organization. Generation of causal networks suggested a reduced Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signaling up to the mitochondria, with the measured gene remodeling of the mitochondrial Ca\n                      <jats:sup>2+<\/jats:sup>\n                      uniporter in favor of enhanced uptake. Histological analyses supported a greater cardiomyocyte hypertrophy and a decreased proximity between the mitochondrial VDAC porin and the reticular IP3-receptor in T2D.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our data support a crucial role for mitochondrial Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signaling in T2D-induced cardiac dysfunction in severe AS patients, from a structural reticulum-mitochondria Ca\n                      <jats:sup>2+<\/jats:sup>\n                      uncoupling to a mitochondrial gene remodeling. Thus, our findings open a new therapeutic avenue to be tested in animal models and further human cardiac biopsies in order to propose new treatments for T2D patients suffering from AS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique Identifier: NCT01862237.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s12933-024-02329-5","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T13:02:47Z","timestamp":1720443767000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Myocardial transcriptomic analysis of diabetic patients with aortic stenosis: key role for mitochondrial calcium signaling"],"prefix":"10.1186","volume":"23","clinical-trial-number":[{"clinical-trial-number":"nct01862237","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Maelle","family":"Cherpaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Meugnier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaultier","family":"Seillier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Pozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Pierrard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Leboube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"Farhat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Vola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Obadia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Amaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Chalabreysse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"May","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Chanon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Brun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Givre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Bidaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Mewton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve","family":"Derumeaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrille","family":"Bergerot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Paillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Thibault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"2329_CR1","unstructured":"https:\/\/diabetesatlas.org\/idfawp\/resource-files\/2021\/07\/IDF_Atlas_10th_Edition_2021.pdf."},{"key":"2329_CR2","doi-asserted-by":"publisher","first-page":"383","DOI":"10.4239\/wjd.v12.i4.383","volume":"12","author":"J Rajbhandari","year":"2021","unstructured":"Rajbhandari J, Fernandez CJ, Agarwal M, Yeap BXY, Pappachan JM. Diabetic heart disease: a clinical update. World J Diabetes. 2021;12:383\u2013406.","journal-title":"World J Diabetes"},{"key":"2329_CR3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/0002-9149(74)90089-7","volume":"34","author":"WB Kannel","year":"1974","unstructured":"Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974;34:29\u201334.","journal-title":"Am J Cardiol"},{"key":"2329_CR4","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12933-018-0728-6","volume":"17","author":"TR Einarson","year":"2018","unstructured":"Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007\u20132017. Cardiovasc Diabetol. 2018;17:83.","journal-title":"Cardiovasc Diabetol"},{"key":"2329_CR5","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1161\/01.CIR.101.19.2271","volume":"101","author":"RB Devereux","year":"2000","unstructured":"Devereux RB, Roman MJ, Paranicas M, O\u2019Grady MJ, Lee ET, Welty TK, et al. Impact of diabetes on cardiac structure and function: the strong heart study. Circulation. 2000;101:2271\u20136.","journal-title":"Circulation"},{"key":"2329_CR6","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12968-018-0472-9","volume":"20","author":"K Yoneyama","year":"2018","unstructured":"Yoneyama K, Venkatesh BA, Wu CO, Mewton N, Gjesdal O, Kishi S, et al. Diabetes mellitus and insulin resistance associate with left ventricular shape and torsion by cardiovascular magnetic resonance imaging in asymptomatic individuals from the multi-ethnic study of atherosclerosis. J Cardiovasc Magn Reson. 2018;20:53.","journal-title":"J Cardiovasc Magn Reson"},{"key":"2329_CR7","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1016\/j.echo.2011.07.017","volume":"24","author":"L Ernande","year":"2011","unstructured":"Ernande L, Bergerot C, Rietzschel ER, De Buyzere ML, Thibault H, PignonBlanc PG, et al. Diastolic dysfunction in patients with type 2 diabetes mellitus: is it really the first marker of diabetic cardiomyopathy? J Am Soc Echocardiogr. 2011;24:1268\u201375.e1.","journal-title":"J Am Soc Echocardiogr"},{"key":"2329_CR8","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1016\/S0195-668X(03)00201-X","volume":"24","author":"B Iung","year":"2003","unstructured":"Iung B. A prospective survey of patients with valvular heart disease in Europe: the euro heart survey on valvular heart disease. Eur Heart J. 2003;24:1231\u201343.","journal-title":"Eur Heart J"},{"key":"2329_CR9","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1016\/j.jacc.2007.08.011","volume":"50","author":"DS Bach","year":"2007","unstructured":"Bach DS, Cimino N, Deeb GM. Unoperated patients with severe aortic stenosis. J Am Coll Cardiol. 2007;50:2018\u20139.","journal-title":"J Am Coll Cardiol"},{"key":"2329_CR10","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.023466","volume":"11","author":"EJ Stein","year":"2022","unstructured":"Stein EJ, Fearon WF, Elmariah S, Kim JB, Kapadia S, Kumbhani DJ, et al. Left ventricular hypertrophy and biomarkers of cardiac damage and stress in aortic stenosis. J Am Heart Assoc. 2022;11:e023466.","journal-title":"J Am Heart Assoc"},{"key":"2329_CR11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s12947-020-0184-9","volume":"18","author":"Y Guo","year":"2020","unstructured":"Guo Y, Sun M, Chen H, Kong D, Shu X, Pan C. Assessment of left ventricular diastolic function after transcatheter aortic valve implantation in aortic stenosis patients by echocardiographic according to different guidelines. Cardiovasc Ultrasound. 2020;18:3.","journal-title":"Cardiovasc Ultrasound"},{"key":"2329_CR12","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1016\/j.athoracsur.2006.07.048","volume":"82","author":"P Varadarajan","year":"2006","unstructured":"Varadarajan P, Kapoor N, Bansal RC, Pai RG. Clinical profile and natural history of 453 nonsurgically managed patients with severe aortic stenosis. Ann Thorac Surg. 2006;82:2111\u20135.","journal-title":"Ann Thorac Surg"},{"key":"2329_CR13","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.jcmg.2018.11.005","volume":"12","author":"J Magne","year":"2019","unstructured":"Magne J, Cosyns B, Popescu BA, Carstensen HG, Dahl J, Desai MY, et al. Distribution and prognostic significance of left ventricular global longitudinal strain in asymptomatic significant aortic stenosis. JACC Cardiovasc Imaging. 2019;12:84\u201392.","journal-title":"JACC Cardiovasc Imaging"},{"key":"2329_CR14","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1161\/CIRCULATIONAHA.111.025270","volume":"124","author":"I Falc\u00e3o-Pires","year":"2011","unstructured":"Falc\u00e3o-Pires I, Hamdani N, Borb\u00e9ly A, Gavina C, Schalkwijk CG, van der Velden J, et al. Diabetes mellitus worsens diastolic left ventricular dysfunction in aortic stenosis through altered myocardial structure and cardiomyocyte stiffness. Circulation. 2011;124:1151\u20139.","journal-title":"Circulation"},{"key":"2329_CR15","first-page":"1815","volume":"108","author":"A Coisne","year":"2022","unstructured":"Coisne A, Montaigne D, Ninni S, Lamblin N, Lemesle G, Delsart P, et al. Diabetes mellitus and cardiovascular mortality across the spectrum of aortic stenosis. Heart Br Card Soc. 2022;108:1815\u201321.","journal-title":"Heart Br Card Soc"},{"key":"2329_CR16","doi-asserted-by":"publisher","first-page":"H2495","DOI":"10.1152\/ajpheart.00139.2008","volume":"295","author":"MJ Raher","year":"2008","unstructured":"Raher MJ, Thibault HB, Buys ES, Kuruppu D, Shimizu N, Brownell A-L, et al. A short duration of high-fat diet induces insulin resistance and predisposes to adverse left ventricular remodeling after pressure overload. Am J Physiol-Heart Circ Physiol. 2008;295:H2495\u2013502.","journal-title":"Am J Physiol-Heart Circ Physiol"},{"key":"2329_CR17","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1161\/CIRCULATIONAHA.122.063444","volume":"148","author":"N Jex","year":"2023","unstructured":"Jex N, Greenwood JP, Cubbon RM, Rider OJ, Chowdhary A, Thirunavukarasu S, et al. Association between type 2 diabetes and changes in myocardial structure, contractile function, energetics, and blood flow before and after aortic valve replacement in patients with severe aortic stenosis. Circulation. 2023;148:1138\u201353.","journal-title":"Circulation"},{"key":"2329_CR18","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1186\/s12933-023-02009-w","volume":"22","author":"E Mart\u00edn-N\u00fa\u00f1ez","year":"2023","unstructured":"Mart\u00edn-N\u00fa\u00f1ez E, Go\u00f1i-Ol\u00f3riz M, Matilla L, Garaikoetxea M, Mourino-Alvarez L, Navarro A, et al. Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach. Cardiovasc Diabetol. 2023;22:280.","journal-title":"Cardiovasc Diabetol"},{"key":"2329_CR19","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1042\/bj1900095","volume":"190","author":"JG McCormack","year":"1980","unstructured":"McCormack JG, Denton RM. Role of calcium ions in the regulation of intramitochondrial metabolism. Properties of the Ca2+-sensitive dehydrogenases within intact uncoupled mitochondria from the white and brown adipose tissue of the rat. Biochem J. 1980;190:95\u2013105.","journal-title":"Biochem J"},{"key":"2329_CR20","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1042\/bj2560403","volume":"256","author":"R Moreno-S\u00e1nchez","year":"1988","unstructured":"Moreno-S\u00e1nchez R, Hansford RG. Dependence of cardiac mitochondrial pyruvate dehydrogenase activity on intramitochondrial free Ca2+ concentration. Biochem J. 1988;256:403\u201312.","journal-title":"Biochem J"},{"key":"2329_CR21","doi-asserted-by":"publisher","first-page":"532","DOI":"10.3389\/fcell.2020.00532","volume":"8","author":"M Rossini","year":"2020","unstructured":"Rossini M, Filadi R. Sarcoplasmic reticulum-mitochondria kissing in cardiomyocytes: Ca2+, ATP, and undisclosed secrets. Front Cell Dev Biol. 2020;8:532.","journal-title":"Front Cell Dev Biol"},{"key":"2329_CR22","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1093\/cvr\/cvw185","volume":"112","author":"LK Seidlmayer","year":"2016","unstructured":"Seidlmayer LK, Kuhn J, Berbner A, Arias-Loza P-A, Williams T, Kaspar M, et al. Inositol 1,4,5-trisphosphate-mediated sarcoplasmic reticulum\u2013mitochondrial crosstalk influences adenosine triphosphate production via mitochondrial Ca2+ uptake through the mitochondrial ryanodine receptor in cardiac myocytes. Cardiovasc Res. 2016;112:491\u2013501.","journal-title":"Cardiovasc Res"},{"key":"2329_CR23","doi-asserted-by":"publisher","first-page":"23343","DOI":"10.1074\/jbc.M116.755496","volume":"291","author":"S De La Fuente","year":"2016","unstructured":"De La Fuente S, Fernandez-Sanz C, Vail C, Agra EJ, Holmstrom K, Sun J, et al. Strategic positioning and biased activity of the mitochondrial calcium uniporter in cardiac muscle. J Biol Chem. 2016;291:23343\u201362.","journal-title":"J Biol Chem"},{"key":"2329_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.echo.2008.11.029","volume":"22","author":"H Baumgartner","year":"2009","unstructured":"Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, Griffin BP, et al. Echocardiographic assessment of valve stenosis: EAE\/ASE recommendations for clinical practice. J Am Soc Echocardiogr. 2009;22:1\u201323.","journal-title":"J Am Soc Echocardiogr"},{"key":"2329_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.echo.2014.10.003","volume":"28","author":"RM Lang","year":"2015","unstructured":"Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American society of echocardiography and the European association of cardiovascular imaging. J Am Soc Echocardiogr. 2015;28:1\u201339.e14.","journal-title":"J Am Soc Echocardiogr"},{"key":"2329_CR26","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/jhh.2009.16","volume":"23","author":"C Cuspidi","year":"2009","unstructured":"Cuspidi C, Meani S, Negri F, Giudici V, Valerio C, Sala C, et al. Indexation of left ventricular mass to body surface area and height to allometric power of 2.7: is the difference limited to obese hypertensives? J Hum Hypertens. 2009;23:728\u201334.","journal-title":"J Hum Hypertens"},{"key":"2329_CR27","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1016\/j.jacc.2009.11.083","volume":"55","author":"A Pag\u00e9","year":"2010","unstructured":"Pag\u00e9 A, Dumesnil JG, Clavel M-A, Chan KL, Teo KK, Tam JW, et al. Metabolic syndrome is associated with more pronounced impairment of left ventricle geometry and function in patients with calcific aortic stenosis. J Am Coll Cardiol. 2010;55:1867\u201374.","journal-title":"J Am Coll Cardiol"},{"key":"2329_CR28","unstructured":"2018 ESC\/ESH Guidelines for the management of arterial hypertension|European Heart Journal|Oxford Academic. https:\/\/academic.oup.com\/eurheartj\/article\/39\/33\/3021\/5079119?login=false. Accessed 14 Mar 2024"},{"key":"2329_CR29","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.echo.2016.01.011","volume":"29","author":"SF Nagueh","year":"2016","unstructured":"Nagueh SF, Smiseth OA, Appleton CP, Byrd BF, Dokainish H, Edvardsen T, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American society of echocardiography and the European association of cardiovascular imaging. J Am Soc Echocardiogr. 2016;29:277\u2013314.","journal-title":"J Am Soc Echocardiogr"},{"key":"2329_CR30","doi-asserted-by":"publisher","first-page":"e34","DOI":"10.1093\/ehjci\/jeab154","volume":"23","author":"OA Smiseth","year":"2022","unstructured":"Smiseth OA, Morris DA, Cardim N, Cikes M, Delgado V, Donal E, et al. Multimodality imaging in patients with heart failure and preserved ejection fraction: an expert consensus document of the European association of cardiovascular imaging. Eur Heart J Cardiovasc Imaging. 2022;23:e34\u201361.","journal-title":"Eur Heart J Cardiovasc Imaging"},{"key":"2329_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.echo.2018.06.004","volume":"32","author":"C Mitchell","year":"2019","unstructured":"Mitchell C, Rahko PS, Blauwet LA, Canaday B, Finstuen JA, Foster MC, et al. Guidelines for performing a comprehensive transthoracic echocardiographic examination in adults: recommendations from the American society of echocardiography. J Am Soc Echocardiogr. 2019;32:1\u201364.","journal-title":"J Am Soc Echocardiogr"},{"key":"2329_CR32","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.jcmg.2022.02.006","volume":"15","author":"EF Davis","year":"2022","unstructured":"Davis EF, Crousillat DR, He W, Andrews CT, Hung JW, Danik JS. Indexing left atrial volumes: alternative indexing methods better predict outcomes in overweight and obese populations. JACC Cardiovasc Imaging. 2022;15:989\u201397.","journal-title":"JACC Cardiovasc Imaging"},{"key":"2329_CR33","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.echo.2016.09.007","volume":"30","author":"F Pathan","year":"2017","unstructured":"Pathan F, D\u2019Elia N, Nolan MT, Marwick TH, Negishi K. Normal ranges of left atrial strain by speckle-tracking echocardiography: a systematic review and meta-analysis. J Am Soc Echocardiogr. 2017;30:59\u201370.e8.","journal-title":"J Am Soc Echocardiogr"},{"key":"2329_CR34","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1016\/j.celrep.2017.02.032","volume":"18","author":"M Paillard","year":"2017","unstructured":"Paillard M, Csord\u00e1s G, Szanda G, Golen\u00e1r T, Debattisti V, Bartok A, et al. Tissue-specific mitochondrial decoding of cytoplasmic Ca2+ signals is controlled by the stoichiometry of MICU1\/2 and MCU. Cell Rep. 2017;18:2291\u2013300.","journal-title":"Cell Rep"},{"key":"2329_CR35","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.3390\/cells12101409","volume":"12","author":"E Frigo","year":"2023","unstructured":"Frigo E, Tommasin L, Lippe G, Carraro M, Bernardi P. The haves and have-nots: the mitochondrial permeability transition pore across species. Cells. 2023;12:1409.","journal-title":"Cells"},{"key":"2329_CR36","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1083\/jcb.200608073","volume":"175","author":"G Szabadkai","year":"2006","unstructured":"Szabadkai G, Bianchi K, V\u00e1rnai P, De Stefani D, Wieckowski MR, Cavagna D, et al. Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J Cell Biol. 2006;175:901\u201311.","journal-title":"J Cell Biol"},{"key":"2329_CR37","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1161\/CIRCRESAHA.121.318241","volume":"128","author":"GD Lopaschuk","year":"2021","unstructured":"Lopaschuk GD, Karwi QG, Tian R, Wende AR, Abel ED. Cardiac energy metabolism in heart failure. Circ Res. 2021;128:1487\u2013513.","journal-title":"Circ Res"},{"key":"2329_CR38","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/S0735-1097(03)00625-9","volume":"42","author":"M Diamant","year":"2003","unstructured":"Diamant M, Lamb HJ, Groeneveld Y, Endert EL, Smit JWA, Bax JJ, et al. Diastolic dysfunction is associatedwith altered myocardial metabolism inasymptomatic normotensive patientswith well-controlled type 2 diabetes mellitus. J Am Coll Cardiol. 2003;42:328\u201335.","journal-title":"J Am Coll Cardiol"},{"key":"2329_CR39","doi-asserted-by":"publisher","first-page":"44","DOI":"10.2337\/db15-0627","volume":"65","author":"E Levelt","year":"2016","unstructured":"Levelt E, Mahmod M, Piechnik SK, Ariga R, Francis JM, Rodgers CT, et al. Relationship between left ventricular structural and metabolic remodelling in type 2 diabetes mellitus. Diabetes. 2016;65:44\u201352.","journal-title":"Diabetes"},{"key":"2329_CR40","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1161\/CIRCULATIONAHA.113.008476","volume":"130","author":"D Montaigne","year":"2014","unstructured":"Montaigne D, Marechal X, Coisne A, Debry N, Modine T, Fayad G, et al. Myocardial contractile dysfunction is associated with impaired mitochondrial function and dynamics in type 2 diabetic but not in obese patients. Circulation. 2014;130:554\u201364.","journal-title":"Circulation"},{"key":"2329_CR41","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1007\/s00395-020-00835-7","volume":"115","author":"M Dia","year":"2020","unstructured":"Dia M, Gomez L, Thibault H, Tessier N, Leon C, Chouabe C, et al. Reduced reticulum\u2013mitochondria Ca2+ transfer is an early and reversible trigger of mitochondrial dysfunctions in diabetic cardiomyopathy. Basic Res Cardiol. 2020;115:74.","journal-title":"Basic Res Cardiol"},{"key":"2329_CR42","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/j.cmet.2013.04.020","volume":"17","author":"G Csord\u00e1s","year":"2013","unstructured":"Csord\u00e1s G, Golen\u00e1r T, Seifert EL, Kamer KJ, Sancak Y, Perocchi F, et al. MICU1 controls both the threshold and cooperative activation of the mitochondrial Ca2+ uniporter. Cell Metab. 2013;17:976\u201387.","journal-title":"Cell Metab"},{"key":"2329_CR43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2022.102618","volume":"105","author":"M Paillard","year":"2022","unstructured":"Paillard M, Huang K-T, Weaver D, Lambert JP, Elrod JW, Hajn\u00f3czky G. Altered composition of the mitochondrial Ca2+ uniporter in the failing human heart. Cell Calcium. 2022;105:102618.","journal-title":"Cell Calcium"},{"key":"2329_CR44","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1093\/cvr\/cvx018","volume":"113","author":"C-R Chong","year":"2017","unstructured":"Chong C-R, Clarke K, Levelt E. Metabolic remodelling in diabetic cardiomyopathy. Cardiovasc Res. 2017;113:422\u201330.","journal-title":"Cardiovasc Res"},{"key":"2329_CR45","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.bbadis.2008.07.003","volume":"1782","author":"J Shearer","year":"2008","unstructured":"Shearer J, Fueger PT, Wang Z, Bracy DP, Wasserman DH, Rottman JN. Metabolic implications of reduced heart-type fatty acid binding protein in insulin resistant cardiac muscle. Biochim Biophys Acta. 2008;1782:586\u201392.","journal-title":"Biochim Biophys Acta"},{"key":"2329_CR46","doi-asserted-by":"publisher","first-page":"34481","DOI":"10.1074\/jbc.M314263200","volume":"279","author":"EJ Murphy","year":"2004","unstructured":"Murphy EJ, Barcelo-Coblijn G, Binas B, Glatz JFC. Heart fatty acid uptake is decreased in heart fatty acid-binding protein gene-ablated mice. J Biol Chem. 2004;279:34481\u20138.","journal-title":"J Biol Chem"},{"key":"2329_CR47","doi-asserted-by":"publisher","first-page":"645","DOI":"10.3390\/antiox12030645","volume":"12","author":"R Rodr\u00edguez-Calvo","year":"2023","unstructured":"Rodr\u00edguez-Calvo R, Granado-Casas M, de P\u00e9rez-Montes A, Julian MT, Domingo M, Codina P, et al. Fatty acid binding proteins 3 and 4 predict both all-cause and cardiovascular mortality in subjects with chronic heart failure and type 2 diabetes mellitus. Antioxidants. 2023;12:645.","journal-title":"Antioxidants"},{"key":"2329_CR48","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/978-3-319-55330-6_11","volume-title":"Mitochondrial dynamics in cardiovascular medicine","author":"HTF di Facundo","year":"2017","unstructured":"di Facundo HTF, Brainard RE, de Caldas FRL, Lucas AMB. Mitochondria and cardiac hypertrophy. In: Santulli G, editor. Mitochondrial dynamics in cardiovascular medicine. Cham: Springer; 2017. p. 203\u20136."},{"key":"2329_CR49","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1161\/CIRCULATIONAHA.121.053575","volume":"144","author":"S Ranjbarvaziri","year":"2021","unstructured":"Ranjbarvaziri S, Kooiker KB, Ellenberger M, Fajardo G, Zhao M, Vander Roest AS, et al. Altered cardiac energetics and mitochondrial dysfunction in hypertrophic cardiomyopathy. Circulation. 2021;144:1714\u201331.","journal-title":"Circulation"},{"key":"2329_CR50","doi-asserted-by":"publisher","first-page":"8339","DOI":"10.1038\/s41598-023-35464-2","volume":"13","author":"Y Luan","year":"2023","unstructured":"Luan Y, Guo G, Luan Y, Yang Y, Yuan R. Single-cell transcriptional profiling of hearts during cardiac hypertrophy reveals the role of MAMs in cardiomyocyte subtype switching. Sci Rep. 2023;13:8339.","journal-title":"Sci Rep"},{"key":"2329_CR51","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1097\/FJC.0000000000001301","volume":"80","author":"Y Wang","year":"2022","unstructured":"Wang Y, Li X, Xu X, Qu X, Yang Y. Transient receptor potential vanilloid type 1 protects against pressure overload-induced cardiac hypertrophy by promoting mitochondria-associated endoplasmic reticulum membranes. J Cardiovasc Pharmacol. 2022;80:430\u201341.","journal-title":"J Cardiovasc Pharmacol"},{"key":"2329_CR52","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.molcel.2017.07.019","volume":"67","author":"DM Arduino","year":"2017","unstructured":"Arduino DM, Wettmarshausen J, Vais H, Navas-Navarro P, Cheng Y, Leimpek A, et al. Systematic identification of MCU modulators by orthogonal interspecies chemical screening. Mol Cell. 2017;67:711\u201323.e7.","journal-title":"Mol Cell"},{"key":"2329_CR53","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109275","volume":"35","author":"A De Mario","year":"2021","unstructured":"De Mario A, Tosatto A, Hill JM, Kriston-Vizi J, Ketteler R, Vecellio Reane D, et al. Identification and functional validation of FDA-approved positive and negative modulators of the mitochondrial calcium uniporter. Cell Rep. 2021;35:109275.","journal-title":"Cell Rep"}],"container-title":["Cardiovascular Diabetology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-024-02329-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12933-024-02329-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-024-02329-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T13:03:25Z","timestamp":1720443805000},"score":1,"resource":{"primary":{"URL":"https:\/\/cardiab.biomedcentral.com\/articles\/10.1186\/s12933-024-02329-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,8]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2329"],"URL":"https:\/\/doi.org\/10.1186\/s12933-024-02329-5","relation":{},"ISSN":["1475-2840"],"issn-type":[{"value":"1475-2840","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,8]]},"assertion":[{"value":"15 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The ethics committee CPP Sud-Est III approved the study 2012-048B on November 2012.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"239"}}