{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:38:34Z","timestamp":1791923914285,"version":"4.3.4"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We investigated myocardial fibrosis in relation to clinical and biochemical characteristics and the metabolomics in patients with primary aldosteronism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Our study included 54 patients with primary aldosteronism. We performed cardiac magnetic resonance to evaluate focal replacement myocardial fibrosis defined as late gadolinium enhancement (LGE) and diffuse interstitial fibrosis as assessed by extracellular volume (ECV) with T1 mapping. We collected information on demographics and data of clinical biomarkers, and performed echocardiography and metabolomic analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with LGE (n=30), compared with those without LGE (n=24), had a longer duration of hypertension, higher 24-hour, daytime and nighttime systolic blood pressure, left ventricular mass index, and plasma NT-proBNP (<jats:italic>P<\/jats:italic>&amp;lt;0.001). However, they had comparable T1 mapping measurements including ECV. LGE significantly (<jats:italic>P \u2264<\/jats:italic> 0.007) and positively correlated with the duration of hypertension, ambulatory systolic blood pressure and LVMI, while ECV and native T1 were significantly (<jats:italic>P \u2264<\/jats:italic> 0.027) and inversely associated with plasma renin activity and positively associated with aldosterone-to-renin ratio. Besides, both LGE and ECV significantly (<jats:italic>P \u2264<\/jats:italic> 0.030) and positively correlated with NT-proBNP. Non-targeted metabolomic analysis showed that the amino-acid metabolism, especially the L-glutamate metabolism, significantly differed between patients with LGE and those without LGE and correlated with blood pressure and echocardiographic measurements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with primary aldosteronism, focal replacement fibrosis was associated with cardiac afterload factors such as blood pressure, while diffuse interstitial fibrosis was associated with hyperaldosteronism. The amino-acid metabolism, especially the L-glutamate metabolism, might be involved in the process of myocardial fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1567876","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T04:15:45Z","timestamp":1746504945000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Myocardial fibrosis in primary aldosteronism"],"prefix":"10.3389","volume":"16","author":[{"given":"Yi-Lin","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Hua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Fei","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Zhong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Min","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Yan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Guang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.01.052","article-title":"Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice","volume":"69","author":"Monticone","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1093\/cvr\/cvy013","article-title":"IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis","volume":"114","author":"Chou","year":"2018","journal-title":"Cardiovasc Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00261.2016","article-title":"Hyperaldosteronism induces left atrial systolic and diastolic dysfunction","volume":"311","author":"Reil","year":"2016","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00097-7","article-title":"Fibrosis of atria and great vessels in response to angiotensin II or aldosterone infusion","volume":"35","author":"Sun","year":"1997","journal-title":"Cardiovasc Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/26.7.671","article-title":"Reactive and reparative myocardial fibrosis in arterial hypertension in the rat","volume":"26","author":"Brilla","year":"1992","journal-title":"Cardiovasc Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000023182.68420.EB","article-title":"Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism","volume":"40","author":"Rossi","year":"2002","journal-title":"Hypertension"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000002146","article-title":"Left atrial myocardial dysfunction in patients with primary aldosteronism as assessed by speckle-tracking echocardiography","volume":"37","author":"Wang","year":"2019","journal-title":"J Hypertens"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000002527","article-title":"A speckle tracking echocardiographic study on right ventricular function in primary aldosteronism","volume":"38","author":"Chen","year":"2020","journal-title":"J Hypertens"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000001534","article-title":"Aldosterone induces left ventricular subclinical systolic dysfunction: a strain imaging study","volume":"36","author":"Chen","year":"2018","journal-title":"J Hypertens"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000002441","article-title":"Prevalence of primary aldosteronism and association with cardiovascular complications in patients with resistant and refractory hypertension","volume":"38","author":"Parasiliti-Caprino","year":"2020","journal-title":"J Hypertens"},{"key":"B11","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s12968-020-00682-4","article-title":"SCMR Position Paper (2020) on clinical indications for cardiovascular magnetic resonance","volume":"22","author":"Leiner","year":"2020","journal-title":"J Cardiovasc Magn Reson"},{"key":"B12","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1016\/j.jacc.2010.11.013","article-title":"Assessment of myocardial fibrosis with cardiovascular magnetic resonance","volume":"57","author":"Mewton","year":"2011","journal-title":"J Am Coll Cardiol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/nrcardio.2014.159","article-title":"Cardiac MRI: A central prognostic tool in myocardial fibrosis","volume":"12","author":"Ambale-Venkatesh","year":"2015","journal-title":"Nat Rev Cardiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.112.974576","article-title":"Demonstration of blood pressure-independent noninfarct myocardial fibrosis in primary aldosteronism: A cardiac magnetic resonance imaging study","volume":"5","author":"Freel","year":"2012","journal-title":"Circ Cardiovasc Imaging"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.23592","article-title":"Contrast-enhanced MRI index of diffuse myocardial fibrosis is increased in primary aldosteronism","volume":"35","author":"Su","year":"2012","journal-title":"J Magn Reson Imaging"},{"key":"B16","doi-asserted-by":"publisher","first-page":"687","DOI":"10.3390\/metabo11100687","article-title":"Metabolic profiling and metabolites fingerprints in human hypertension: discovery and potential","volume":"11","author":"Onuh","year":"2021","journal-title":"Metabolites"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-4061","article-title":"The management of primary aldosteronism: Case detection, diagnosis, and treatment: An Endocrine Society clinical practice guideline","volume":"101","author":"Funder","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B18","article-title":"Aldosterone-to-renin ratio threshold for screening primary aldosteronism in Chinese hypertensive patients","volume":"34","author":"Chen","year":"2006","journal-title":"Zhonghua Xin Xue Guan Bing Za Zhi"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000002510","article-title":"Genetics, prevalence, screening and confirmation of primary aldosteronism: A position statement and consensus of the Working Group on Endocrine Hypertension of The European Society of Hypertension","volume":"38","author":"Mulatero","year":"2020","journal-title":"J Hypertens"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41440-023-01482-w","article-title":"Non-invasive left ventricular pressure-strain loop study on cardiac fibrosis in primary aldosteronism: A comparative study with cardiac magnetic resonance imaging","volume":"47","author":"Chen","year":"2024","journal-title":"Hypertens Res"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.echo.2014.10.003","article-title":"Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging","volume":"28","author":"Lang","year":"2015","journal-title":"J Am Soc Echocardiogr"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1161\/hc0402.102975","article-title":"Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association","volume":"105","author":"Cerqueira","year":"2002","journal-title":"Circulation"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03697","article-title":"Association of longitudinal changes in left ventricular structure and function with myocardial fibrosis: The Multi-Ethnic Study of Atherosclerosis study","volume":"64","author":"Ambale Venkatesh","year":"2014","journal-title":"Hypertension"},{"key":"B24","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.ijcard.2015.02.008","article-title":"Galectin-3 and myocardial fibrosis in nonischemic dilated cardiomyopathy","volume":"184","author":"Vergaro","year":"2015","journal-title":"Int J Cardiol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00690-0","article-title":"Blood pressure and its variability: classic and novel measurement techniques","volume":"19","author":"Schutte","year":"2022","journal-title":"Nat Rev Cardiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.08.064","article-title":"Noninvasive detection of fibrosis applying contrast-enhanced cardiac magnetic resonance in different forms of left ventricular hypertrophy relation to remodeling","volume":"53","author":"Rudolph","year":"2009","journal-title":"J Am Coll Cardiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/nrcardio.2012.158","article-title":"Myofibroblast-mediated mechanisms of pathological remodelling of the heart","volume":"10","author":"Weber","year":"2013","journal-title":"Nat Rev Cardiol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.10.044","article-title":"Association of elevated NT-proBNP with myocardial fibrosis in the Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"70","author":"Liu","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2013.04.060","article-title":"Usefulness of high-sensitivity cardiac troponin T and brain natriuretic peptide as biomarkers of myocardial fibrosis in patients with hypertrophic cardiomyopathy","volume":"112","author":"Kawasaki","year":"2013","journal-title":"Am J Cardiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.3390\/ijms23042111","article-title":"Atrial fibrillation and aortic ectasia as complications of primary aldosteronism: Focus on pathophysiological aspects","volume":"23","author":"Bollati","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2165\/11593690-000000000-00000","article-title":"Left heart morphology and function in primary aldosteronism","volume":"19","author":"Milan","year":"2012","journal-title":"High Blood Press Cardiovasc Prev"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.122.19134","article-title":"Cardiac structure and function across the spectrum of aldosteronism: The Atherosclerosis Risk in Communities Study","volume":"79","author":"Brown","year":"2022","journal-title":"Hypertension"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2020.06.026","article-title":"Aldosterone-related myocardial extracellular matrix expansion in hypertension in humans: A proof-of-concept study by cardiac magnetic resonance","volume":"13","author":"Redheuil","year":"2020","journal-title":"JACC Cardiovasc Imaging"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01316","article-title":"Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism","volume":"62","author":"Rossi","year":"2013","journal-title":"Hypertension"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2020.04.026","article-title":"Extracellular volume and global longitudinal strain both associate with outcomes but correlate minimally","volume":"13","author":"Fr\u00f6jdh","year":"2020","journal-title":"JACC Cardiovasc Imaging"},{"key":"B36","doi-asserted-by":"publisher","first-page":"103173","DOI":"10.1016\/j.arcmed.2024.103173","article-title":"Fibroblast plasticity in pulmonary and cardiovascular fibrosis: Mechanistic insights and emerging therapeutic targets","volume":"56","author":"Cabrera-Fuentes","year":"2025","journal-title":"Arch Med Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.057879","article-title":"Glutaminolysis is essential for myofibroblast persistence and in vivo targeting reverses fibrosis and cardiac dysfunction in heart failure","volume":"145","author":"Gibb","year":"2022","journal-title":"Circulation"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1053\/j.gastro.2017.12.022","article-title":"Hedgehog-YAP signaling pathway regulates glutaminolysis to control activation of hepatic stellate cells","volume":"154","author":"Du","year":"2018","journal-title":"Gastroenterology"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000444","article-title":"Glutaminolysis is required for transforming growth factor-\u03b21-induced myofibroblast differentiation and activation","volume":"293","author":"Bernard","year":"2018","journal-title":"J Biol Chem"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-022-02252-0","article-title":"GDH promotes isoprenaline-induced cardiac hypertrophy by activating mTOR signaling via elevation of \u03b1-ketoglutarate level","volume":"395","author":"Lin","year":"2022","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2360-19.2020","article-title":"Tumor necrosis factor \u03b1 receptor type 1 activation in the hypothalamic paraventricular nucleus contributes to glutamate signaling and angiotensin II-dependent hypertension","volume":"41","author":"Woods","year":"2021","journal-title":"J Neurosci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00692.2021","article-title":"Inhibition of glutaminase 1-mediated glutaminolysis improves pathological cardiac remodeling","volume":"322","author":"Yoshikawa","year":"2022","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"114930","DOI":"10.1016\/j.biopha.2023.114930","article-title":"Vitamin A metabolites inhibit ferroptosis","volume":"164","author":"Jakaria","year":"2023","journal-title":"BioMed Pharmacother"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1038\/s41467-023-36837-x","article-title":"Retinol dehydrogenase 10 reduction mediated retinol metabolism disorder promotes diabetic cardiomyopathy in male mice","volume":"14","author":"Wu","year":"2023","journal-title":"Nat Commun"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1567876\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T04:15:46Z","timestamp":1746504946000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1567876\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":44,"alternative-id":["10.3389\/fendo.2025.1567876"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1567876","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,6]]},"article-number":"1567876"}}