Show simple item record Mátyás, Csaba Németh, Balázs Tamás Oláh, Attila Hidi, László Birtalan, Ede Kellermayer, Dalma Ruppert, Mihály Korkmaz-Icoz S Kökény, Gábor Horvath, Eszter Mária Szabó, Gábor Balázs Merkely, Béla Péter Radovits, Tamás 2018-06-21T13:41:41Z 2018-06-21T13:41:41Z 2015
dc.identifier 84946490282
dc.identifier.citation pagination=145, pages 13; journalVolume=14; journalIssueNumber=1; journalTitle=CARDIOVASCULAR DIABETOLOGY;
dc.identifier.uri doi:10.1186/s12933-015-0309-x
dc.description.abstract BACKGROUND: Diabetes mellitus (DM) leads to the development of diabetic cardiomyopathy, which is associated with altered nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signalling. Cardioprotective effects of elevated intracellular cGMP-levels have been described in different heart diseases. In the current study we aimed at investigating the effects of pharmacological activation of sGC in diabetic cardiomyopathy. METHODS: Type-1 DM was induced in rats by streptozotocin. Animals were treated either with the sGC activator cinaciguat (10 mg/kg/day) or with placebo orally for 8 weeks. Left ventricular (LV) pressure-volume (P-V) analysis was used to assess cardiac performance. Additionally, gene expression (qRT-PCR) and protein expression analysis (western blot) were performed. Cardiac structure, markers of fibrotic remodelling and DNA damage were examined by histology, immunohistochemistry and TUNEL assay, respectively. RESULTS: DM was associated with deteriorated cGMP signalling in the myocardium (elevated phosphodiesterase-5 expression, lower cGMP-level and impaired PKG activity). Cardiomyocyte hypertrophy, fibrotic remodelling and DNA fragmentation were present in DM that was associated with impaired LV contractility (preload recruitable stroke work (PRSW): 49.5 +/- 3.3 vs. 83.0 +/- 5.5 mmHg, P < 0.05) and diastolic function (time constant of LV pressure decay (Tau): 17.3 +/- 0.8 vs. 10.3 +/- 0.3 ms, P < 0.05). Cinaciguat treatment effectively prevented DM related molecular, histological alterations and significantly improved systolic (PRSW: 66.8 +/- 3.6 mmHg) and diastolic (Tau: 14.9 +/- 0.6 ms) function. CONCLUSIONS: Cinaciguat prevented structural, molecular alterations and improved cardiac performance of the diabetic heart. Pharmacological activation of sGC might represent a new therapy approach for diabetic cardiomyopathy.
dc.relation.ispartof urn:issn:1475-2840
dc.title The soluble guanylate cyclase activator cinaciguat prevents cardiac dysfunction in a rat model of type-1 diabetes mellitus
dc.type Journal Article 2018-06-13T15:12:22Z
dc.language.rfc3066 en
dc.identifier.mtmt 2966649
dc.identifier.wos 000363923300001
dc.identifier.pubmed 26520063
dc.contributor.department SE/AOK/K/Fül-Orr-Gégészeti és Fej-Nyaksebészeti Klinika
dc.contributor.department SE/AOK/I/Kórélettani Intézet
dc.contributor.department SE/AOK/I/Élettani Intézet
dc.contributor.department SE/AOK/K/VAROSMAJOR_SZÍVÉRGYÓGY/Kardiológia Központ - Kardiológiai Tanszék [2017.10.31]
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote Béla Merkely and Tamás Radovits contributed equally to this study

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