dc.contributor.author |
Mátyás, Csaba |
|
dc.contributor.author |
Németh, Balázs Tamás |
|
dc.contributor.author |
Oláh, Attila |
|
dc.contributor.author |
Hidi, László |
|
dc.contributor.author |
Birtalan, Ede |
|
dc.contributor.author |
Kellermayer, Dalma |
|
dc.contributor.author |
Ruppert, Mihály |
|
dc.contributor.author |
Korkmaz-Icoz S |
|
dc.contributor.author |
Kökény, Gábor |
|
dc.contributor.author |
Horvath, Eszter Mária |
|
dc.contributor.author |
Szabó, Gábor Balázs |
|
dc.contributor.author |
Merkely, Béla Péter |
|
dc.contributor.author |
Radovits, Tamás |
|
dc.date.accessioned |
2018-06-21T13:41:41Z |
|
dc.date.available |
2018-06-21T13:41:41Z |
|
dc.date.issued |
2015 |
|
dc.identifier |
84946490282 |
|
dc.identifier.citation |
pagination=145, pages 13;
journalVolume=14;
journalIssueNumber=1;
journalTitle=CARDIOVASCULAR DIABETOLOGY; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/5607 |
|
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 |
|
dc.date.updated |
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 |
|