{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:56:39Z","timestamp":1791942999518,"version":"4.3.4"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,3,24]]},"abstract":"\n Background<\/jats:title>\n \n Diabetes mellitus (\n DM<\/jats:styled-content>\n ) has multifactorial detrimental effects on myocardial tissue. Recently, carbonic anhydrases (\n CAs<\/jats:styled-content>\n ) have been shown to play a major role in diabetic microangiopathy but their role in the diabetic cardiomyopathy is still unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We obtained left ventricular samples from patients with\n DM<\/jats:styled-content>\n type 2 (DM\u2010T2) and nondiabetic (\n NDM<\/jats:styled-content>\n ) patients with postinfarct heart failure who were undergoing surgical coronary revascularization. Myocardial levels of\n CA<\/jats:styled-content>\n \u2010I and CA\u2010\n II<\/jats:styled-content>\n were 6\u2010 and 11\u2010fold higher, respectively, in\n DM<\/jats:styled-content>\n \u2010T2 versus\n NDM<\/jats:styled-content>\n patients. Elevated\n CA<\/jats:styled-content>\n \u2010I expression was mainly localized in the cardiac interstitium and endothelial cells.\n CA<\/jats:styled-content>\n \u2010I induced by high glucose levels hampers endothelial cell permeability and determines endothelial cell apoptosis in vitro. Accordingly, capillary density was significantly lower in the\n DM<\/jats:styled-content>\n \u2010T2 myocardial samples (mean\u00b1\n SE<\/jats:styled-content>\n =2152\u00b1146 versus 4545\u00b1211\/mm\n 2<\/jats:sup>\n ). On the other hand, CA\u2010II was mainly upregulated in cardiomyocytes. The latter was associated with sodium\u2010hydrogen exchanger\u20101 hyperphosphorylation, exaggerated myocyte hypertrophy (cross\u2010sectional area 565\u00b134 versus 412\u00b127\u00a0\u03bcm\n 2<\/jats:sup>\n ), and apoptotic death (830\u00b154 versus 470\u00b134 per 10\n 6<\/jats:sup>\n myocytes) in\n DM<\/jats:styled-content>\n \u2010T2 versus\n NDM<\/jats:styled-content>\n patients. CA\u2010II is activated by high glucose levels and directly induces cardiomyocyte hypertrophy and death in vitro, which are prevented by sodium\u2010hydrogen exchanger\u20101 inhibition. CA\u2010II was shown to be a direct target for repression by micro\n RNA<\/jats:styled-content>\n \u201023b, which was downregulated in myocardial samples from\n DM<\/jats:styled-content>\n \u2010T2 patients. MicroRNA\u201023b is regulated by p38 mitogen\u2010activated protein kinase, and it modulates high\u2010glucose CA\u2010II\u2013dependent effects on cardiomyocyte survival in vitro.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Myocardial\n CA<\/jats:styled-content>\n activation is significantly elevated in human diabetic ischemic cardiomyopathy. These data may open new avenues for targeted treatment of diabetic heart failure.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.113.000434","type":"journal-article","created":{"date-parts":[[2014,3,27]],"date-time":"2014-03-27T03:27:18Z","timestamp":1395890838000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":91,"title":["Carbonic Anhydrase Activation Is Associated With Worsened Pathological Remodeling in Human Ischemic Diabetic Cardiomyopathy"],"prefix":"10.1161","volume":"3","author":[{"given":"Daniele","family":"Torella","sequence":"first","affiliation":[{"name":"Molecular and Cellular Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy"},{"name":"Stem Cell and Regenerative Biology Unit (BioStem), Faculty of Sciences, Liverpool John Moores University, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina M.","family":"Ellison","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy"},{"name":"Centre of Human and Aerospace Physiological Sciences & Centre for Stem Cells and Regenerative Medicine, King's College London, School of Biomedical Sciences, Guys campus, London, SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Torella","sequence":"additional","affiliation":[{"name":"Department of Cardio\u2010Thoracic and Respiratory Sciences, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Vicinanza","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy"},{"name":"Stem Cell and Regenerative Biology Unit (BioStem), Faculty of Sciences, Liverpool John Moores University, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda","family":"Aquila","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Iaconetti","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Scalise","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Marino","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverley J.","family":"Henning","sequence":"additional","affiliation":[{"name":"Stem Cell and Regenerative Biology Unit (BioStem), Faculty of Sciences, Liverpool John Moores University, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona C.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Centre of Human and Aerospace Physiological Sciences & Centre for Stem Cells and Regenerative Medicine, King's College London, School of Biomedical Sciences, Guys campus, London, SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarice","family":"Gareri","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Lascar","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Internal and Experimental Medicine \u2018Lanzara\u2010Magrassi\u2019, Second University of Naples, Naples, Italy"},{"name":"Center of Cardiovascular Excellence, Second University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Cuda","sequence":"additional","affiliation":[{"name":"Laboratory of Proteomics and Mass Spectrometry, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Salvatore","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Internal and Experimental Medicine \u2018Lanzara\u2010Magrassi\u2019, Second University of Naples, Naples, Italy"},{"name":"Center of Cardiovascular 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