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001-es BibID:	BIBFORM070057
035-os BibID:	(Wos)000397857700007 (Scopus)85007236091
Első szerző:	Mátyás Csaba
Cím:	Prevention of the development of heart failure with preserved ejection fraction by the phosphodiesterase-5A inhibitor vardenafil in rats with type 2 diabetes / Mátyás Csaba, Németh Balázs T., Oláh Attila, Török Marianna, Ruppert Mihály, Kellermayer Dalma, Barta Bálint A., Szabó Gábor, Kökény Gábor, Horváth Eszter M., Bódi Beáta, Papp Zoltán, Merkely Béla, Radovits Tamás
Dátum:	2017
ISSN:	1388-9842
Megjegyzések:	Heart failure with preserved ejection fraction (HFpEF) has a great epidemiological burden. The pathophysiological role of cyclic guanosine monophosphate (cGMP) signalling has been intensively investigated in HFpEF. Elevated levels of cGMP have been shown to exert cardioprotective effects in various cardiovascular diseases, including diabetic cardiomyopathy. We investigated the effect of long-term preventive application of the phosphodiesterase-5A (PDE5A) inhibitor vardenafil in diabetic cardiomyopathy-associated HFpEF. METHODS AND RESULTS: Zucker diabetic fatty (ZDF) rats were used as a model of HFpEF and ZDF lean rats served as controls. Animals received vehicle or 10 mg/kg body weight vardenafil per os from weeks 7 to 32 of age. Cardiac function, morphology was assessed by left ventricular (LV) pressure-volume analysis and echocardiography at week 32. Cardiomyocyte force measurements were performed. The key markers of cGMP signalling, nitro-oxidative stress, apoptosis, myocardial hypertrophy and fibrosis were examined. The ZDF animals showed diastolic dysfunction (increased LV/cardiomyocyte stiffness, prolonged LV relaxation time), preserved systolic performance, decreased myocardial cGMP level coupled with impaired protein kinase G (PKG) activity, increased nitro-oxidative stress, enhanced cardiomyocyte apoptosis, and hypertrophic and fibrotic remodelling of the myocardium. Vardenafil effectively prevented the development of HFpEF by maintaining diastolic function (decreased LV/cardiomyocyte stiffness and LV relaxation time), by restoring cGMP levels and PKG activation, by lowering apoptosis and by alleviating nitro-oxidative stress, myocardial hypertrophy and fibrotic remodelling. CONCLUSIONS: We report that vardenafil successfully prevented the development of diabetes mellitus-associated HFpEF. Thus, PDE5A inhibition as a preventive approach might be a promising option in the management of HFpEF patients with diabetes mellitus.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	European Journal Of Heart Failure. - 19 : 3 (2017), p. 326-336. -
További szerzők:	Németh Balázs Tamás Oláh Attila (sebész) Török Marianna Ruppert Mihály Kellermayer Dalma Barta Bálint András Szabó Gábor (orvos) Kökény Gábor Horváth Eszter Mária Bódi Beáta (1989-) (molekuláris biológus) Papp Zoltán (1965-) (kardiológus, élettanász) Merkely Béla (1965-) (orvos) Radovits Tamás
Pályázati támogatás:	OTKA-K 109083 OTKA TÁMOP 4.2.4. A/1-11-1-2012-0001 TÁMOP
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001-es BibID:	BIBFORM085958
Első szerző:	Ruppert Mihály
Cím:	A miofilamentáris rendszer Ca2+-érzékenysége korrellál a bal kamrai kontraktilitással a fokozott nyomásterhelés által előidézett patológiás szívizom-hipertrófia patkánymodelljében / Ruppert Mihály, Bódi Beáta, Nagy Dávid, Korkmaz-Icöz Sevil, Loganathan Sivakkanan, Oláh Attila, Barta Bálint András, Sayour Alex Ali, Benke Kálmán, Karck Matthias, Merkely Béla, Papp Zoltán, Szabó Gábor, Radovits Tamás
Dátum:	2019
ISSN:	0133-5596
Tárgyszavak:	Orvostudományok Elméleti orvostudományok magyar nyelvű folyóiratközlemény hazai lapban folyóiratcikk contractility myocardial hypertrophy
Megjelenés:	Cardiologia Hungarica. - 49 : 2 (2019), p. 88-99. -
További szerzők:	Bódi Beáta (1989-) (molekuláris biológus) Nagy Dávid Korkmaz-Icöz, Sevil Loganathan, Sivakkanan Oláh Attila (sebész) Barta Bálint András Sayour, Alex Ali Benke Kálmán Karck, Matthias Merkely Béla (1965-) (orvos) Papp Zoltán (1965-) (kardiológus, élettanász) Szabó Gábor Radovits Tamás
Pályázati támogatás:	GINOP-2.3.2-15-2016-00048 GINOP
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001-es BibID:	BIBFORM077811
035-os BibID:	(WoS)000466833500022 (Scopus)85062460292
Első szerző:	Ruppert Mihály
Cím:	Myofilament Ca2+ sensitivity correlates with left ventricular contractility during the progression of pressure overload-induced left ventricular myocardial hypertrophy in rats / Mihály Ruppert, Beáta Bódi, Sevil Korkmaz-Icöz, Sivakkanan Loganathan, Weipeng Jiang, Lorenz Lehmann, Attila Oláh, Bálint András Barta, Alex Ali Sayour, Béla Merkely, Matthias Karck, Zoltán Papp, Gábor Szabó, Tamás Radovits
Dátum:	2019
ISSN:	0022-2828
Megjegyzések:	AIM: Here we aimed at investigating the relation between left ventricular (LV) contractility and myofilament function during the development and progression of pressure overload (PO)-induced LV myocardial hypertrophy (LVH). METHODS: Abdominal aortic banding (AB) was performed to induce PO in rats for 6, 12 and 18?weeks. Sham operated animals served as controls. Structural and molecular alterations were investigated by serial echocardiography, histology, quantitative real-time PCR and western blot. LV function was assessed by pressure-volume analysis. Force measurement was carried out in permeabilized cardiomyocytes. RESULTS: AB resulted in the development of pathological LVH as indicated by increased heart weight-to-tibial length ratio, LV mass index, cardiomyocyte diameter and fetal gene expression. These alterations were already present at early stage of LVH (AB-week6). Furthermore, at more advanced stages (AB-week12, AB-week18), myocardial fibrosis and chamber dilatation were also observed. From a hemodynamic point of view, the AB-wk6 group was associated with increased LV contractility, maintained ventriculo-arterial coupling (VAC) and preserved systolic function. In the same experimental group, increased myofilament Ca2+ sensitivity (pCa50) and hyperphosphorylation of cardiac troponin-I (cTnI) at Threonine-144 was detected. In contrast, in the AB-wk12 and AB-wk18 groups, the initial augmentation of LV contractility, as well as the increased myofilament Ca2+ sensitivity and cTnI (Threonine-144) hyperphosphorylation diminished, leading to impaired VAC and reduced systolic performance. Strong correlation was found between LV contractility parameters and myofilament Ca2+-sensitivity among the study groups.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Ca(2+) sensitivity Contractility Myocardial hypertrophy Myofilament function
Megjelenés:	Journal of Molecular and Cellular Cardiology. - 129 (2019), p. 208-218. -
További szerzők:	Bódi Beáta (1989-) (molekuláris biológus) Korkmaz-Icöz, Sevil Loganathan, Sivakkanan Jiang, Weipeng Lehmann, Lorenz Oláh Attila (sebész) Barta Bálint András Sayour, Alex Ali Merkely Béla (1965-) (orvos) Karck, Matthias Papp Zoltán (1965-) (kardiológus, élettanász) Szabó Gábor (orvos) Radovits Tamás
Pályázati támogatás:	ÚNKP-18-3-I-SE-9 ÚNKP ÚNKP-18-3-III-DE-387 ÚNKP NVKP-16-1-2016-0017 Egyéb GINOP-2.3.2-15-2016-00048 GINOP OTKA11003 OTKA
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