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1.
001-es BibID:
BIBFORM095647
035-os BibID:
(cikkazonosító)1708 (WoS)000676633500001 (Scopus)85114067373
Első szerző:
Bánhegyi Viktor (kardiológus)
Cím:
Human Tissue Angiotensin Converting Enzyme (ACE) Activity Is Regulated by Genetic Polymorphisms, Posttranslational Modifications, Endogenous Inhibitors and Secretion in the Serum, Lungs and Heart / Viktor Bánhegyi, Attila Enyedi Gábor Áron Fülöp, Attila Oláh, Ivetta Mányiné Siket, Csongor Váradi, Klaudia Bottyán, Mária Lódi, Alexandra Csongrádi, Azeem J. Umar, Miklós Fagyas, Dániel Czuriga, István Édes, Miklós Pólos, Béla Merkely, Zoltán Csanádi, Zoltán Papp, Gábor Szabó, Tamás Radovits, István Takács, Attila Tóth
Dátum:
2021
ISSN:
2073-4409
Megjegyzések:
Objective: Inhibitors of the angiotensin converting enzyme (ACE) are the primarily chosen drugs to treat heart failure and hypertension. Moreover, an imbalance in tissue ACE/ACE2 activity is implicated in COVID-19. In the present study, we tested the relationships between circulating and tissue (lung and heart) ACE levels in men. Methods: Serum, lung (n = 91) and heart (n = 72) tissue samples were collected from Caucasian patients undergoing lung surgery or heart transplantation. ACE I/D genotype, ACE concentration and ACE activity were determined from serum and tissue samples. Clinical parameters were also recorded. Results: A protocol for ACE extraction was developed for tissue ACE measurements. Extraction of tissue-localized ACE was optimal in a 0.3% Triton-X-100 containing buffer, resulting in 260 ? 12% higher ACE activity over detergent-free conditions. SDS or higher Triton-X-100 concentrations inhibited the ACE activity. Serum ACE concentration correlated with ACE I/D genotype (II: 166 ? 143 ng/mL, n = 19, ID: 198 ? 113 ng/mL, n = 44 and DD: 258 ? 109 ng/mL, n = 28, p < 0.05) as expected. In contrast, ACE expression levels in the lung tissue were approximately the same irrespective of the ACE I/D genotype (II: 1423 ? 1276 ng/mg, ID: 1040 ? 712 ng/mg and DD: 930 ? 1273 ng/mg, p > 0.05) in the same patients (values are in median ? IQR). Moreover, no correlations were found between circulating and lung tissue ACE concentrations and activities (Spearman's p > 0.05). In contrast, a significant correlation was identified between ACE activities in serum and heart tissues (Spearman's Rho = 0.32, p < 0.01). Finally, ACE activities in lung and the serum were endogenously inhibited to similar degrees (i.e., to 69 ? 1% and 53 ? 2%, respectively). Conclusion: Our data suggest that circulating ACE activity correlates with left ventricular ACE, but not with lung ACE in human. More specifically, ACE activity is tightly coordinated by genotype-dependent expression, endogenous inhibition and secretion mechanisms.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
angiotenzin konvertáló enzim
szív
tüdő
reguláció
szöveti
keringő
Megjelenés:
Cells. - 10 : 7 (2021), p. 1-13. -
További szerzők:
Enyedi Attila (1975-) (sebész)
Fülöp Gábor Áron (1988-) (általános orvos)
Oláh Attila (sebész)
Mányiné Siket Ivetta (1962-) (laborasszisztens)
Váradi Csongor (1984-) (sebész, mellkassebész szakorvos)
Bottyán Klaudia
Lódi Mária (1991-)
Csongrádi Alexandra (1990-) (molekuláris biológus)
Umar, Muhammad Azeem Jalil
Fagyas Miklós (1984-) (orvos)
Czuriga Dániel (1982-) (kardiológus)
Édes István (1952-) (kardiológus)
Pólos Miklós
Merkely Béla (1965-) (orvos)
Csanádi Zoltán (1960-) (kardiológus)
Papp Zoltán (1965-) (kardiológus, élettanász)
Szabó Gábor (orvos)
Radovits Tamás
Takács István (1963-) (sebész)
Tóth Attila (1971-) (biológus)
Pályázati támogatás:
GINOP-2.2.1-15-2017-00043
GINOP
ÚNKP-18-3-III-DE-209
Egyéb
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:
2.
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
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:
3.
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
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:
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