dc.contributor.author |
Ruppert, Mihály |
|
dc.contributor.author |
Korkmaz-Icöz, Sevil |
|
dc.contributor.author |
Li, Shiliang |
|
dc.contributor.author |
Brlecic, Paige |
|
dc.contributor.author |
Németh, Balázs Tamás |
|
dc.contributor.author |
Oláh, Attila |
|
dc.contributor.author |
Horváth, Eszter M |
|
dc.contributor.author |
Veres, Gábor |
|
dc.contributor.author |
Pleger, Sven |
|
dc.contributor.author |
Grabe, Niels |
|
dc.contributor.author |
Merkely, Béla |
|
dc.contributor.author |
Karck, Matthias |
|
dc.contributor.author |
Radovits, Tamás |
|
dc.contributor.author |
Szabó, Gábor |
|
dc.date.accessioned |
2020-03-20T12:27:51Z |
|
dc.date.available |
2020-03-20T12:27:51Z |
|
dc.date.issued |
2019 |
|
dc.identifier |
85065496758 |
|
dc.identifier.citation |
journalVolume=9;pagination=1869, pages: 16;journalTitle=FRONTIERS IN PHYSIOLOGY;journalAbbreviatedTitle=FRONT PHYSIOL; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/8182 |
|
dc.identifier.uri |
doi:10.3389/fphys.2018.01869 |
|
dc.description.abstract |
Background: Pressure unloading induces the regression of left ventricular myocardial hypertrophy (LVH). Recent findings indicate that pharmacological activation of the soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) pathway may also exert reverse-remodeling properties in the myocardium. Therefore, we aimed to investigate the effects of the sGC activator cinaciguat in a rat model of LVH and compare it to the "gold standard" pressure unloading therapy. Methods: Abdominal aortic banding was performed for 6 or 12 weeks. Sham operated animals served as controls. Pressure unloading was induced by removing the aortic constriction after week 6. The animals were treated from week 7 to 12, with 10 mg/kg/day cinaciguat or with placebo p.o., respectively. Cardiac function and morphology were assessed by left ventricular pressure-volume analysis and echocardiography. Additionally, key markers of myocardial hypertrophy, fibrosis, nitro-oxidative stress, apoptosis and cGMP signaling were analyzed. Results: Pressure unloading effectively reversed LVH, decreased collagen accumulation and provided protection against oxidative stress and apoptosis. Regression of LVH was also associated with a full recovery of cardiac function. In contrast, chronic activation of the sGC enzyme by cinaciguat at sustained pressure overload only slightly influenced pre-established hypertrophy. However, it led to increased PKG activity and had a significant impact on interstitial fibrosis, nitro-oxidative stress and apoptosis. Amelioration of the pathological structural alterations prevented the deterioration of LV systolic function (contractility and ejection fraction) and improved myocardial stiffness. Conclusion: Our results indicate that both cinaciguat treatment and pressure unloading evoked anti-remodeling effects and improved LV function, however in a differing manners. |
|
dc.relation.ispartof |
urn:issn:1664-042X |
|
dc.title |
Comparison of the Reverse-Remodeling Effect of Pharmacological Soluble Guanylate Cyclase Activation With Pressure Unloading in Pathological Myocardial Left Ventricular Hypertrophy |
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dc.type |
Journal Article |
|
dc.date.updated |
2020-02-05T10:01:18Z |
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dc.language.rfc3066 |
en |
|
dc.rights.holder |
NULL |
|
dc.identifier.mtmt |
30408874 |
|
dc.identifier.wos |
000455140800001 |
|
dc.identifier.pubmed |
30670980 |
|
dc.contributor.department |
SE/AOK/K/VAROSMAJOR_SZÍVÉRGYÓGY/Kardiológia Központ - Kardiológiai Tanszék |
|
dc.contributor.department |
SE/AOK/I/Élettani Intézet |
|
dc.contributor.institution |
Semmelweis Egyetem |
|
dc.mtmt.swordnote |
Radovits T és Szabó G megosztott utolsó szerzők. |
|