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4. Truncated titin is structurally integrated into the human dilated cardiomyopathic sarcomere

Author

Kellermayer, Dalma, Tordai, Hedvig, Kiss, Balazs, Torok, Gyorgy, Peter, Daniel M., Sayour, Alex Ali, Polos, Miklos, Hartyanszky, Istvan, Szilveszter, Balint, Labeit, Siegfried, Gango, Ambrus, Bedics, Gabor, Bodor, Csaba, Radovits, Tamas, Merkely, Bela, and Kellermayer, Miklos S.Z.

Subjects
Gene mutations -- Research, Cardiomyopathy, Dilated -- Development and progression -- Causes of -- Genetic aspects, Cardiovascular research, Muscle proteins -- Health aspects -- Structure -- Genetic aspects, Striated muscle -- Genetic aspects -- Health aspects, Health care industry
Abstract

Heterozygous (HET) truncating variant mutations in the TTN gene (TTNtvs), encoding the giant titin protein, are the most common genetic cause of dilated cardiomyopathy (DCM). However, the molecular mechanisms by which TTNtv mutations induce DCM are controversial. Here, we studied 127 clinically identified DCM human cardiac samples with next- generation sequencing (NGS), high-resolution gel electrophoresis, Western blot analysis, and super-resolution microscopy in order to dissect the structural and functional consequences of TTNtv mutations. The occurrence of TTNtv was found to be 15% in the DCM cohort. Truncated titin proteins matching, by molecular weight, the gene sequence predictions were detected in the majority of the [TTNtv.sup.+] samples. Full-length titin was reduced in [TTNtv.sup.+] compared with [TTNtv.sup.-] samples. Proteomics analysis of washed myofibrils and stimulated emission depletion (STED) super- resolution microscopy of myocardial sarcomeres labeled with sequence-specific anti-titin antibodies revealed that truncated titin was structurally integrated into the sarcomere. Sarcomere length-dependent anti-titin epitope position, shape, and intensity analyses pointed at possible structural defects in the I/A junction and the M-band of [TTNtv.sup.+] sarcomeres, which probably contribute, possibly via faulty mechanosensor function, to the development of manifest DCM., Introduction The giant myofilament titin is the third most abundant sarcomeric protein besides actin and myosin (1). A single titin molecule spans half of the sarcomere from the Z-disk to [...]

Published
2024
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7. A Comparative Investigation of the Pulmonary Vasodilating Effects of Inhaled NO Gas Therapy and Inhalation of a New Drug Formulation Containing a NO Donor Metabolite (SIN-1A).

Author

Oláh, Attila, Barta, Bálint András, Ruppert, Mihály, Sayour, Alex Ali, Nagy, Dávid, Bálint, Tímea, Nagy, Georgina Viktória, Puskás, István, Szente, Lajos, Szőcs, Levente, Sohajda, Tamás, Zima, Endre, Merkely, Béla, and Radovits, Tamás

Subjects
RESPIRATORY therapy, PULMONARY artery catheters, ADULT respiratory distress syndrome, PULMONARY hypertension, COVID-19, CYCLODEXTRIN derivatives
Abstract

Numerous research projects focused on the management of acute pulmonary hypertension as Coronavirus Disease 2019 (COVID-19) might lead to hypoxia-induced pulmonary vasoconstriction related to acute respiratory distress syndrome. For that reason, inhalative therapeutic options have been the subject of several clinical trials. In this experimental study, we aimed to examine the hemodynamic impact of the inhalation of the SIN-1A formulation (N-nitroso-N-morpholino-amino-acetonitrile, the unstable active metabolite of molsidomine, stabilized by a cyclodextrin derivative) in a porcine model of acute pulmonary hypertension. Landrace pigs were divided into the following experimental groups: iNO (inhaled nitric oxide, n = 3), SIN-1A-5 (5 mg, n = 3), and SIN-1A-10 (10 mg, n = 3). Parallel insertion of a PiCCO system and a pulmonary artery catheter (Swan-Ganz) was performed for continuous hemodynamic monitoring. The impact of iNO (15 min) and SIN-1A inhalation (30 min) was investigated under physiologic conditions and U46619-induced acute pulmonary hypertension. Mean pulmonary arterial pressure (PAP) was reduced transiently by both substances. SIN-1A-10 had a comparable impact compared to iNO after U46619-induced pulmonary hypertension. PAP and PVR decreased significantly (changes in PAP: −30.1% iNO, −22.1% SIN-1A-5, −31.2% SIN-1A-10). While iNO therapy did not alter the mean arterial pressure (MAP) and systemic vascular resistance (SVR), SIN-1A administration resulted in decreased MAP and SVR values. Consequently, the PVR/SVR ratio was markedly reduced in the iNO group, while SIN-1A did not alter this parameter. The pulmonary vasodilatory impact of inhaled SIN-1A was shown to be dose-dependent. A larger dose of SIN-1A (10 mg) resulted in decreased PAP and PVR in a similar manner to the gold standard iNO therapy. Inhalation of the nebulized solution of the new SIN-1A formulation (stabilized by a cyclodextrin derivative) might be a valuable, effective option where iNO therapy is not available due to dosing difficulties or availability. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Truncated titin is structurally integrated into the human dilated cardiomyopathic sarcomere

Author

Kellermayer, Dalma, primary, Tordai, Hedvig, additional, Kiss, Balázs, additional, Török, György, additional, Péter, Dániel M., additional, Sayour, Alex Ali, additional, Pólos, Miklós, additional, Hartyánszky, István, additional, Szilveszter, Bálint, additional, Labeit, Siegfried, additional, Gángó, Ambrus, additional, Bedics, Gábor, additional, Bödör, Csaba, additional, Radovits, Tamás, additional, Merkely, Bela, additional, and Kellermayer, Miklós S.Z., additional

Published
2023
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15. Preservation solution Custodiol containing human alpha-1-antitrypsin improves graft recovery after prolonged cold ischemic storage in a rat model of heart transplantation

Author

Korkmaz-Icöz, Sevil, primary, Abulizi, Sophia, additional, Li, Kunsheng, additional, Korkmaz, Brice, additional, Georgevici, Adrian-Iustin, additional, Sayour, Alex Ali, additional, Loganathan, Sivakkanan, additional, Canoglu, Hansa, additional, Karck, Matthias, additional, and Szabó, Gábor, additional

Published
2023
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19. Truncated titin is integrated into the human dilated cardiomyopathic sarcomere

Author

Kellermayer, Dalma, primary, Tordai, Hedvig, additional, Kiss, Balazs, additional, Török, György, additional, Sayour, Alex A., additional, Pólos, Miklós, additional, Hartyánszky, István, additional, Szilveszter, Bálint, additional, Labeit, Siegfried, additional, Gángó, Ambrus, additional, Bedics, Gábor, additional, Bödör, Csaba, additional, Radovits, Tamás, additional, Merkely, Béla, additional, and Kellermayer, Miklós, additional

Published
2023
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23. Sex similarities and differences in the reverse and anti-remodeling effect of pressure unloading therapy in a rat model of aortic banding and debanding

Author

Ruppert, Mihály, primary, Barta, Bálint András, additional, Korkmaz-Icöz, Sevil, additional, Loganathan, Sivakkanan, additional, Oláh, Attila, additional, Sayour, Alex Ali, additional, Benke, Kálmán, additional, Nagy, Dávid, additional, Bálint, Tímea, additional, Karck, Matthias, additional, Schilling, Oliver, additional, Merkely, Béla, additional, Radovits, Tamás, additional, and Szabó, Gábor, additional

Published
2022
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24. Arterial graft preservation with an endothelial damage inhibitor reduces vascular dysfunction in a rat model of in vitro ischemia/reperfusion injury

Author

Ballikaya, Belinda, primary, Soethoff, Jasmin, additional, Kraft, Patricia, additional, Sayour, Alex, additional, Radovits, Tamás, additional, Loganathan, Sivakkanan, additional, Karck, Matthias, additional, Veres, Gábor, additional, Szabó, Gábor, additional, and Korkmaz-Icöz, Sevil, additional

Published
2022
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28. Abstract 13054: Longitudinal Strain-Derived Myocardial Work to Reflect the Systolic Performance of Athlete’s Heart

Author

Tokodi, Marton, primary, Oláh, Attila, additional, Fabian, Alexandra, additional, Lakatos, Balint K, additional, Hizoh, István, additional, Ruppert, Mihály, additional, Sayour, Alex A, additional, Barta, Balint A, additional, Kiss, Orsolya, additional, Sydó, Nóra, additional, Csulak, Emese, additional, Ladanyi, Zsuzsanna, additional, Merkely, Béla, additional, Kovacs, Attila, additional, and Radovits, Tamás, additional

Published
2021
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31. Left Ventricular Pressure-Strain-Volume Loops for the Noninvasive Assessment of Volume Overload-Induced Myocardial Dysfunction

Author

Tokodi, Márton, primary, Lakatos, Bálint K., additional, Ruppert, Mihály, additional, Fábián, Alexandra, additional, Oláh, Attila, additional, Sayour, Alex A., additional, Ladányi, Zsuzsanna, additional, Soós, András, additional, Merkely, Béla, additional, Sengupta, Partho P., additional, Radovits, Tamás, additional, and Kovács, Attila, additional

Published
2021
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32. Novel insights into the athlete’s heart: is myocardial work the new champion of systolic function?

Author

Tokodi, Márton, primary, Oláh, Attila, additional, Fábián, Alexandra, additional, Lakatos, Bálint Károly, additional, Hizoh, István, additional, Ruppert, Mihály, additional, Sayour, Alex Ali, additional, Barta, Bálint András, additional, Kiss, Orsolya, additional, Sydó, Nóra, additional, Csulak, Emese, additional, Ladányi, Zsuzsanna, additional, Merkely, Béla, additional, Kovács, Attila, additional, and Radovits, Tamás, additional

Published
2021
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33. Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart Failure

Author

Sayour, Alex Ali, primary, Ruppert, Mihály, additional, Oláh, Attila, additional, Benke, Kálmán, additional, Barta, Bálint András, additional, Zsáry, Eszter, additional, Ke, Haoran, additional, Horváth, Eszter Mária, additional, Merkely, Béla, additional, and Radovits, Tamás, additional

Published
2021
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34. The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats

Author

Korkmaz-Icöz, Sevil, primary, Kocer, Cenk, additional, Sayour, Alex A., additional, Kraft, Patricia, additional, Benker, Mona I., additional, Abulizi, Sophia, additional, Georgevici, Adrian-Iustin, additional, Brlecic, Paige, additional, Radovits, Tamás, additional, Loganathan, Sivakkanan, additional, Karck, Matthias, additional, and Szabó, Gábor, additional

Published
2021
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35. AIM2-driven inflammasome activation in heart failure

Author

Onódi, Zsófia, primary, Ruppert, Mihály, additional, Kucsera, Dániel, additional, Sayour, Alex Ali, additional, Tóth, Viktória E, additional, Koncsos, Gábor, additional, Novák, Julianna, additional, Brenner, Gábor B, additional, Makkos, András, additional, Baranyai, Tamás, additional, Giricz, Zoltán, additional, Görbe, Anikó, additional, Leszek, Przemyslaw, additional, Gyöngyösi, Mariann, additional, Horváth, Iván G, additional, Schulz, Rainer, additional, Merkely, Béla, additional, Ferdinandy, Péter, additional, Radovits, Tamás, additional, and Varga, Zoltán V, additional

Published
2021
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36. Conditioned Medium from Mesenchymal Stem Cells Alleviates Endothelial Dysfunction of Vascular Grafts Submitted to Ischemia/Reperfusion Injury in 15-Month-Old Rats

Author

Korkmaz-Icöz, Sevil, primary, Sun, Xiaoxin, additional, Li, Shiliang, additional, Brlecic, Paige, additional, Loganathan, Sivakkanan, additional, Ruppert, Mihály, additional, Sayour, Alex Ali, additional, Radovits, Tamás, additional, Karck, Matthias, additional, and Szabó, Gábor, additional

Published
2021
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37. Additional file 1 of Sex-related differences of early cardiac functional and proteomic alterations in a rat model of myocardial ischemia

Author

Barta, B��lint Andr��s, Ruppert, Mih��ly, Fr��hlich, Klemens Erwin, Cosenza-Contreras, Miguel, Ol��h, Attila, Sayour, Alex Ali, Kov��cs, Kriszti��n, Karvaly, Gell��rt Bal��zs, Biniossek, Martin, Merkely, B��la, Schilling, Oliver, and Radovits, Tam��s

Abstract

Additional file 1: Fig. S1. Validation of LC���MS/MS measurements with western blot. A���D: Relative protein expression of VASP, POSTN, OPN and ATP2A2 as measured by LC���MS/MS and western blot. Values were normalized to the mean of the corresponding control group. Statistical significance of post hoc test compared to same-sex control is highlighted as follows: *P

Published
2021
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38. Additional file 1 of Mesenchymal stem cell-derived conditioned medium protects vascular grafts of brain-dead rats against in vitro ischemia/reperfusion injury

Author

Korkmaz-Icöz, Sevil, Pengyu Zhou, Yuxing Guo, Sivakkanan Loganathan, Brlecic, Paige, Radovits, Tamás, Sayour, Alex Ali, Ruppert, Mihály, Veres, Gábor, Karck, Matthias, and Szabó, Gábor

Abstract

Additional file 1. : Online Table 1: Sequence of primers for real-time PCR and Universal Probe Library (UPL) probes.

Published
2021
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39. Additional file 2 of Sex-related differences of early cardiac functional and proteomic alterations in a rat model of myocardial ischemia

Author

Barta, B��lint Andr��s, Ruppert, Mih��ly, Fr��hlich, Klemens Erwin, Cosenza-Contreras, Miguel, Ol��h, Attila, Sayour, Alex Ali, Kov��cs, Kriszti��n, Karvaly, Gell��rt Bal��zs, Biniossek, Martin, Merkely, B��la, Schilling, Oliver, and Radovits, Tam��s

Abstract

Additional file 2: Table S1. Results of differential expression analysis performed with Limma.

Published
2021
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41. Myocardial work index: a marker of left ventricular contractility in pressure‐ or volume overload‐induced heart failure

Author

Lakatos, Bálint Károly, primary, Ruppert, Mihály, additional, Tokodi, Márton, additional, Oláh, Attila, additional, Braun, Szilveszter, additional, Karime, Christian, additional, Ladányi, Zsuzsanna, additional, Sayour, Alex Ali, additional, Barta, Bálint András, additional, Merkely, Béla, additional, Radovits, Tamás, additional, and Kovács, Attila, additional

Published
2021
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42. Balanced Intense Exercise Training Induces Atrial Oxidative Stress Counterbalanced by the Antioxidant System and Atrial Hypertrophy That Is Not Associated with Pathological Remodeling or Arrhythmogenicity

Author

Oláh, Attila, primary, Barta, Bálint András, additional, Sayour, Alex Ali, additional, Ruppert, Mihály, additional, Virág-Tulassay, Eszter, additional, Novák, Julianna, additional, Varga, Zoltán V., additional, Ferdinandy, Péter, additional, Merkely, Béla, additional, and Radovits, Tamás, additional

Published
2021
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43. Novel insights into the athlete's heart: is myocardial work the new champion of systolic function?

Author

Tokodi, Márton, Oláh, Attila, Fábián, Alexandra, Lakatos, Bálint Károly, Hizoh, István, Ruppert, Mihály, Sayour, Alex Ali, Barta, Bálint András, Kiss, Orsolya, Sydó, Nóra, Csulak, Emese, Ladányi, Zsuzsanna, Merkely, Béla, Kovács, Attila, and Radovits, Tamás

Subjects
LEFT heart ventricle, ECHOCARDIOGRAPHY, EXERCISE tests, AEROBIC capacity, BLOOD pressure, CARDIOPULMONARY system, ANIMAL experimentation, CARDIAC contraction, RATS, DESCRIPTIVE statistics, HEART physiology, REACTIVE oxygen species, OXYGEN in the body
Abstract

Aims We sought to investigate the correlation between speckle-tracking echocardiography (STE)-derived myocardial work (MW) and invasively measured contractility in a rat model of athlete's heart. We also assessed MW in elite athletes and explored its association with cardiopulmonary exercise test (CPET)-derived aerobic capacity. Methods and results Sixteen rats underwent a 12-week swim training program and were compared to controls (n  = 16). STE was performed to assess global longitudinal strain (GLS), which was followed by invasive pressure-volume analysis to measure contractility [slope of end-systolic pressure–volume relationship (ESPVR)]. Global MW index (GMWI) was calculated from GLS curves and left ventricular (LV) pressure recordings. In the human investigations, 20 elite swimmers and 20 healthy sedentary controls were enrolled. GMWI was calculated through the simultaneous evaluation of GLS and non-invasively approximated LV pressure curves at rest. All subjects underwent CPET to determine peak oxygen uptake (VO2/kg). Exercised rats exhibited higher values of GLS, GMWI, and ESPVR than controls (−20.9 ± 1.7 vs. −17.6 ± 1.9%, 2745 ± 280 vs. 2119 ± 272 mmHg·%, 3.72 ± 0.72 vs. 2.61 ± 0.40 mmHg/μL, all P Exercise < 0.001). GMWI correlated robustly with ESPVR (r  = 0.764, P  < 0.001). In humans, regular exercise training was associated with decreased GLS (−17.6 ± 1.5 vs. −18.8 ± 0.9%, P Exercise = 0.002) but increased values of GMWI at rest (1899 ± 136 vs. 1755 ± 234 mmHg·%, P Exercise = 0.025). GMWI exhibited a positive correlation with VO2/kg (r  = 0.527, P  < 0.001). Conclusions GMWI precisely reflected LV contractility in a rat model of exercise-induced LV hypertrophy and captured the supernormal systolic performance in human athletes even at rest. Our findings endorse the utilization of MW analysis in the evaluation of the athlete's heart. [ABSTRACT FROM AUTHOR]

Published
2022
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44. Az akut canagliflozinkezelés kivédi a miokardiális iszkémia-reperfúziós károsodást patkánymodellen

Author

Sayour, Alex Ali, primary, Ruppert, Mihály, additional, Oláh, Attila, additional, Benke, Kálmán, additional, Benkő, Rita, additional, Horváth, Eszter Mária, additional, Korkmaz-Icöz, Sevil, additional, Loganathan, Sivakkanan, additional, Karck, Matthias, additional, Merkely, Béla, additional, Szabó, Gábor, additional, and Radovits, Tamás, additional

Published
2020
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45. Sex Differences in Morphological and Functional Aspects of Exercise-Induced Cardiac Hypertrophy in a Rat Model

Author

Oláh, Attila, primary, Mátyás, Csaba, additional, Kellermayer, Dalma, additional, Ruppert, Mihály, additional, Barta, Bálint András, additional, Sayour, Alex Ali, additional, Török, Marianna, additional, Koncsos, Gábor, additional, Giricz, Zoltáng, additional, Ferdinandy, Péter, additional, Merkely, Béla, additional, and Radovits, Tamás, additional

Published
2019
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46. A miofilamentáris rendszer Ca2+-érzékenysége korrellál a bal kamrai kontraktilitással a fokozott nyomásterhelés által előidézett patológiás szívizom-hipertrófia patkánymodelljében

Author

Ruppert, Mihály, primary, Bódi, Beáta, additional, Nagy, Dávid, additional, Korkmaz-Icöz, Sevil, additional, Loganathan, Sivakkanan, additional, Oláh, Attila, additional, Barta, Bálint András, additional, Sayour, Alex Ali, additional, Benke, Kálmán, additional, Karck, Matthias, additional, Merkely, Béla, additional, Papp, Zoltán, additional, Szabó, Gábor, additional, and Radovits, Tamás, additional

Published
2019
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47. Pressure-volume analysis reveals characteristic sex-related differences in cardiac function in a rat model of aortic banding-induced myocardial hypertrophy

Author

Ruppert, Mihály, primary, Korkmaz-Icöz, Sevil, additional, Loganathan, Sivakkanan, additional, Jiang, Weipeng, additional, Lehmann, Lorenz, additional, Oláh, Attila, additional, Sayour, Alex Ali, additional, Barta, Bálint András, additional, Merkely, Béla, additional, Karck, Matthias, additional, Radovits, Tamás, additional, and Szabó, Gábor, additional

Published
2018
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48. Impairment of the Akt pathway in transplanted Type 1 diabetic hearts is associated with post-transplant graft injury†

Author

Korkmaz-Icöz, Sevil, primary, Li, Shiliang, additional, Loganathan, Sivakkanan, additional, Radovits, Tamás, additional, Ruppert, Mihály, additional, Brlecic, Paige, additional, Sayour, Alex Ali, additional, Veres, Gábor, additional, Fleming, Thomas, additional, Brune, Maik, additional, Most, Patrick, additional, Karck, Matthias, additional, and Szabó, Gábor, additional

Published
2018
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49. A hipertrófiás myocardium reverz elektromos remodellációjának vizsgálata patkánymodellben

Author

Ruppert, Mihály, primary, Barta, Bálint András, additional, Korkmaz-Icöz, Sevil, additional, Li, Shiliang, additional, Oláh, Attila, additional, Mátyás, Csaba, additional, Németh, Balázs Tamás, additional, Benke, Kálmán, additional, Sayour, Alex Ali, additional, Karck, Matthias, additional, Merkely, Béla, additional, Radovits, Tamás, additional, and Szabó, Gábor, additional

Published
2018
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50. A hasonló fokú fiziológiás és patológiás balkamra-hipertrófia különböző in vivo hemodinamikai következményekhez vezet

Author

Oláh, Attila, primary, Sayour, Alex Ali, additional, Németh, Balázs Tamás, additional, Mátyás, Csaba, additional, Hidi, László, additional, Lux, Árpád, additional, Ruppert, Mihály, additional, Kellermayer, Dalma, additional, Szabó, Lilla, additional, Török, Marianna, additional, Meltzer, Anna, additional, Gellér, László, additional, Merkely, Béla, additional, and Radovits, Tamás, additional

Published
2018
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