{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:21:54Z","timestamp":1791944514118,"version":"4.3.4"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":684,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,1,21]],"date-time":"2024-01-21T00:00:00Z","timestamp":1705795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Cardiac remodelling plays a major role in the prognosis of patients with aortic stenosis (AS) and could impact the benefits of aortic valve replacement. Our study aimed to evaluate the expression of sodium\u2013glucose cotransporter 2 (SGLT2) gene and protein in patients with severe AS stratified in high gradient (HG) and low flow-low gradient (LF-LG) AS and its association with cardiac functional impairments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Gene expression and protein levels of main biomarkers of cardiac fibrosis (galectin-3, sST2, serpin-4, procollagen type I amino-terminal peptide, procollagen type I carboxy-terminal propeptide, collagen, transforming growth factor [TGF]-\u03b2), inflammation (growth differentiation factor-15, interleukin-6, nuclear factor-\u03baB [NF-\u03baB]), oxidative stress (superoxide dismutase 1 [SOD1] and 2 [SOD2]), and cardiac metabolism (sodium\u2013hydrogen exchanger, peroxisome proliferator-activated receptor [PPAR]-\u03b1, PPAR-\u03b3, glucose transporter 1 [GLUT1] and 4 [GLUT4]) were evaluated in blood samples and heart biopsies of 45 patients with AS. Our study showed SGLT2 gene and protein hyper-expression in patients with LF-LG AS, compared to controls and HG AS (p\u2009&amp;lt;\u20090.05). These differences remained significant even after adjusting for age, gender, body mass index, history of diabetes mellitus, arterial hypertension, and coronary artery disease. SGLT2 gene expression was positively correlated with: (i) TGF-\u03b2 (r\u2009=\u20090.72, p\u2009&amp;lt;\u20090.001) and collagen (r\u2009=\u20090.73, p\u2009&amp;lt;\u20090.001) as markers of fibrosis; (ii) NF-\u03baB (r\u2009=\u20090.36, p\u2009&amp;lt;\u20090.01) and myocardial interleukin-6 (r\u2009=\u20090.68, p\u2009&amp;lt;\u20090.001) as markers of inflammation: (iii) SOD2 (r\u2009=\u2009\u22120.38, p\u2009&amp;lt;\u20090.006) as a marker of oxidative stress; (iv) GLUT4 (r\u2009=\u20090.33, p\u2009&amp;lt;\u20090.02) and PPAR-\u03b1 (r\u2009=\u20090.36, p\u2009&amp;lt;\u20090.01) as markers of cardiac metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients with LF-LG AS, SGLT2 gene and protein were hyper-expressed in cardiomyocytes and associated with myocardial fibrosis, inflammation, and oxidative stress.<\/jats:p>\n                  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