{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:03:33Z","timestamp":1790485413625,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T00:00:00Z","timestamp":1602201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PON03PE_00078_1 and PON03PE_00078_2"],"award-info":[{"award-number":["PON03PE_00078_1 and PON03PE_00078_2"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Clinical management of diabetic cardiomyopathy represents an unmet need owing to insufficient knowledge about the molecular mechanisms underlying the dysfunctional heart. The aim of this work is to better clarify the role of matrix metalloproteinase 2 (MMP-2) isoforms and of translocator protein (TSPO)\/voltage-dependent anion-selective channel 1 (VDAC1) modulation in the development of hyperglycaemia-induced myocardial injury. Hyperglycaemia was induced in Sprague-Dawley rats through a streptozocin injection (35 mg\/Kg, i.p.). After 60 days, cardiac function was analysed by echocardiography. Nicotinamide Adenine Dinucleotide Phosphate NADPH oxidase and TSPO expression was assessed by immunohistochemistry. MMP-2 activity was detected by zymography. Superoxide anion production was estimated by MitoSOX\u2122 staining. Voltage-dependent anion-selective channel 1 (VDAC-1), B-cell lymphoma 2 (Bcl-2), and cytochrome C expression was assessed by Western blot. Hyperglycaemic rats displayed cardiac dysfunction; this response was characterized by an overexpression of NADPH oxidase, accompanied by an increase of superoxide anion production. Under hyperglycaemia, increased expression of TSPO and VDAC1 was detected. MMP-2 downregulated activity occurred under hyperglycemia and this profile of activation was accompanied by the translocation of intracellular N-terminal truncated isoform of MMP-2 (NT-MMP-2) from mitochondria-associated membrane (MAM) into mitochondria. In the onset of diabetic cardiomyopathy, mitochondrial impairment in cardiomyocytes is characterized by the dysregulation of the different MMP-2 isoforms. This can imply the generation of a \u201cfrail\u201d myocardial tissue unable to adapt itself to stress.<\/jats:p>","DOI":"10.3390\/ijms21207432","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T10:19:23Z","timestamp":1602238763000},"page":"7432","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Role of TSPO\/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats"],"prefix":"10.3390","volume":"21","author":[{"given":"Micaela","family":"Gliozzi","sequence":"first","affiliation":[{"name":"IRC-FSH Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Renato Dulbecco Institute, Presso Fondazione Terina, 88046 Lamezia Terme (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Scarano","sequence":"additional","affiliation":[{"name":"IRC-FSH Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Renato Dulbecco Institute, Presso Fondazione Terina, 88046 Lamezia Terme (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Musolino","sequence":"additional","affiliation":[{"name":"IRC-FSH Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Renato Dulbecco Institute, Presso Fondazione Terina, 88046 Lamezia Terme (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Carresi","sequence":"additional","affiliation":[{"name":"IRC-FSH Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Renato 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Caterina","family":"Zito","sequence":"additional","affiliation":[{"name":"IRC-FSH Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Renato Dulbecco Institute, Presso Fondazione Terina, 88046 Lamezia Terme (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saverio","family":"Nucera","sequence":"additional","affiliation":[{"name":"IRC-FSH Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Renato Dulbecco Institute, Presso Fondazione Terina, 88046 Lamezia Terme (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bosco","sequence":"additional","affiliation":[{"name":"IRC-FSH Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Renato Dulbecco Institute, Presso Fondazione Terina, 88046 Lamezia Terme (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Maiuolo","sequence":"additional","affiliation":[{"name":"IRC-FSH Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Renato Dulbecco Institute, Presso Fondazione Terina, 88046 Lamezia Terme (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Macr\u00ec","sequence":"additional","affiliation":[{"name":"IRC-FSH Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Renato Dulbecco Institute, Presso Fondazione Terina, 88046 Lamezia Terme (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Guarnieri","sequence":"additional","affiliation":[{"name":"IRC-FSH Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Renato 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