{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T11:41:38Z","timestamp":1792928498279,"version":"4.5.0"},"reference-count":84,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T00:00:00Z","timestamp":1562025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The high incidence and poor prognosis of heart failure (HF) patients affected with diabetes (DM) is in part related to a specific cardiac remodeling currently recognized as diabetic cardiomyopathy (DCM). This cardiac frame occurs regardless of the presence of coronary artery diseases (CAD) and it can account for 15\u201320% of the total diabetic population. The pathogenesis of DCM remains controversial, and several molecular and cellular alterations including myocardial hypertrophy, interstitial fibrosis, oxidative stress and vascular inflammation, have been postulated. The main cardio-vascular alterations associated with hyperglycemia comprise endothelial dysfunction, adverse effects of circulating free fatty acids (FFA) and increased systemic inflammation. High glucose concentrations lead to a loss of mitochondrial networks, increased reactive oxygen species (ROS), endothelial nitric oxide synthase (eNOS) activation and a reduction in cGMP production related to protein kinase G (PKG) activity. Current mechanisms enhance the collagen deposition with subsequent increased myocardial stiffness. Several concerns regarding the exact role of DCM in HF development such as having an appearance as either dilated or as a concentric phenotype and whether diabetes could be considered a causal factor or a comorbidity in HF, remain to be clarified. In this review, we sought to explain the different DCM subtypes and the underlying pathophysiological mechanisms. Therefore, the traditional and new molecular and signal alterations and their relationship with macroscopic structural abnormalities are described.<\/jats:p>","DOI":"10.3390\/ijms20133264","type":"journal-article","created":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T12:11:17Z","timestamp":1562069477000},"page":"3264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":135,"title":["Molecular Dysfunction and Phenotypic Derangement in Diabetic Cardiomyopathy"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3828-1624","authenticated-orcid":false,"given":"Isabella","family":"Evangelista","sequence":"first","affiliation":[{"name":"Cardiovascular Diseases Unit, Department of Internal Medicine, Le Scotte Hospital University of Siena, Viale Bracci, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranuccio","family":"Nuti","sequence":"additional","affiliation":[{"name":"Cardiovascular Diseases Unit, Department of Internal Medicine, Le Scotte Hospital University of Siena, Viale Bracci, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Picchioni","sequence":"additional","affiliation":[{"name":"Cardiovascular Diseases Unit, Department of Internal Medicine, Le Scotte Hospital University of Siena, Viale Bracci, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Dotta","sequence":"additional","affiliation":[{"name":"Diabetes Unit, Department of Medicine, Surgery and Neurosciences, Le Scotte Hospital University of Siena, Viale Bracci, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Palazzuoli","sequence":"additional","affiliation":[{"name":"Cardiovascular Diseases Unit, Department of Internal Medicine, Le Scotte Hospital University of Siena, Viale Bracci, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1093\/eurheartj\/ehv134","article-title":"Clinical diabetic cardiomyopathy: A two-faced disease with restrictive and dilated phenotypes","volume":"36","author":"Seferovic","year":"2015","journal-title":"Eur. 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