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001-es BibID:	BIBFORM098750
035-os BibID:	(cikkazonosító)1776
Első szerző:	Bódi Beáta (molekuláris biológus)
Cím:	Long-Term PDE-5A Inhibition Improves Myofilament Function in Left and Right Ventricular Cardiomyocytes through Partially Different Mechanisms in Diabetic Rat Hearts / Bódi Beáta, Kovács Árpád, Gulyás Hajnalka, Mártha Lilla, Tóth Attila, Mátyás Csaba, Barta Bálint András, Oláh Attila, Merkely Béla, Radovits Tamás, Papp Zoltán
Dátum:	2021
ISSN:	2076-3921
Megjegyzések:	Heart failure with preserved ejection fraction (HFpEF) and right ventricular (RV) dysfunction are frequent complications of diabetic cardiomyopathy. Here we aimed to characterize RV and left ventricular (LV) remodeling and its prevention by vardenafil (a long-acting phosphodiesterase5A (PDE-5A) inhibitor) administration in a diabetic HFpEF model. Zucker Diabetic Fatty (ZDF) and control, ZDF Lean (Lean) male rats received 10 mg/kg vardenafil (ZDF + Vard; Lean + Vard) per os, on a daily basis for a period of 25 weeks. In vitro force measurements, biochemical and histochemical assays were employed to assess cardiomyocyte function and signaling. Vardenafil treatment increased cyclic guanosine monophosphate (cGMP) levels and decreased 3-nitrotyrosine (3-NT) levels in the left and right ventricles of ZDF animals, but not in Lean animals. Cardiomyocyte passive tension (Fpassive) was higher in LV and RV cardiomyocytes of ZDF rats than in those receiving preventive vardenafil treatment. Levels of overall titin phosphorylation did not differ in the four experimental groups. Maximal Ca2+-activated force (Fmax) of LV and RV cardiomyocytes were preserved in ZDF animals. Ca2+-sensitivity of isometric force production (pCa50) was significantly higher in LV (but not in RV) cardiomyocytes of ZDF rats than in their counterparts in the Lean or Lean + Vard groups. In accordance, the phosphorylation levels of cardiac troponin I (cTnI) and myosin binding protein-C (cMyBP-C) were lower in LV (but not in RV) cardiomyocytes of ZDF animals than in their counterparts of the Lean or Lean + Vard groups. Vardenafil treatment normalized pCa50 values in LV cardiomyocytes, and it decreased pCa50 below control levels in RV cardiomyocytes in the ZDF + Vard group. Our data illustrate partially overlapping myofilament protein alterations for LV and RV cardiomyocytes in diabetic rat hearts upon long-term PDE-5A inhibition. While uniform patterns in cGMP, 3-NT and Fpassive levels predict identical effects of vardenafil therapy for the diastolic function in both ventricles, the uneven cTnI, cMyBP-C phosphorylation levels and pCa50 values implicate different responses for the systolic function.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk right ventricle HFpEF diabetic cardiomyopathy cardiomyocyte passive tension Ca2+ - sensitivity of force production myofilament protein phosphorylation vardenafil phosphodiesterase-5A
Megjelenés:	Antioxidants. - 10 : 11 (2021), p. 1-13. -
További szerzők:	Kovács Árpád (1986-) (kardiológus) Gulyás Hajnalka Mártha Lilla Tóth Attila (1971-) (biológus) Mátyás Csaba Barta Bálint András Oláh Attila Merkely Béla (1965-) (orvos) Radovits Tamás Papp Zoltán (1965-) (kardiológus, élettanász)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00043 GINOP TKP2020-IKA-04 Egyéb TKP2020-NKA-04 Egyéb 2020-4.1.1-TKP2020 Egyéb NVKP_16-1-2016-0017 Egyéb
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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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