TY - JOUR AU - Heger, Jacqueline AU - Partsch, Stefan AU - Harjung, Claudia AU - Varga, Zoltán AU - Baranyai, Tamás AU - Weiß, Johannes AU - Kremer, Lea AU - Locquet, Fabian AU - Leszek, Przemyslaw AU - Ágg, Bence AU - Benczik, Bettina AU - Ferdinandy, Péter AU - Schulz, Rainer AU - Euler, Gerhild TI - YB-1 Is a Novel Target for the Inhibition of α-Adrenergic-Induced Hypertrophy JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 1 PG - 19 SN - 1661-6596 DO - 10.3390/ijms25010401 UR - https://m2.mtmt.hu/api/publication/34474992 ID - 34474992 N1 - Funding Agency and Grant Number: European Union's Horizon 2020 research and innovation program [739593]; National Research, Development, and Innovation Fund of Hungary [NVKP_16-1-2016-0017, VEKOP-2.3.2-16-2016-00002, 2020-1.1.6-JOVO-2021-00013]; Ministry for Innovation and Technology in Hungary [RRF-2.3.1-21-2022-00003]; European Union Funding text: This research was funded by the European Union's Horizon 2020 research and innovation program under grant agreement No. 739593; the National Research, Development, and Innovation Fund of Hungary (NVKP_16-1-2016-0017-'National Heart Program'; VEKOP-2.3.2-16-2016-00002, 2020-1.1.6-JOVO-2021-00013); and the Thematic Excellence Programme (2020-4.1.1.-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the TherapeuticDevelopment and Bioimaging thematic programs of Semmelweis University. Project No. RRF-2.3.1-21-2022-00003 has been implemented with support provided by the European Union. AB - Cardiac hypertrophy resulting from sympathetic nervous system activation triggers the development of heart failure. The transcription factor Y-box binding protein 1 (YB-1) can interact with transcription factors involved in cardiac hypertrophy and may thereby interfere with the hypertrophy growth process. Therefore, the question arises as to whether YB-1 influences cardiomyocyte hypertrophy and might thereby influence the development of heart failure. YB-1 expression is downregulated in human heart biopsies of patients with ischemic cardiomyopathy (n = 8), leading to heart failure. To study the impact of reduced YB-1 in cardiac cells, we performed small interfering RNA (siRNA) experiments in H9C2 cells as well as in adult cardiomyocytes (CMs) of rats. The specificity of YB-1 siRNA was analyzed by a miRNA-like off-target prediction assay identifying potential genes. Testing three high-scoring genes by transfecting cardiac cells with YB-1 siRNA did not result in downregulation of these genes in contrast to YB-1, whose downregulation increased hypertrophic growth. Hypertrophic growth was mediated by PI3K under PE stimulation, as well by downregulation with YB-1 siRNA. On the other hand, overexpression of YB-1 in CMs, caused by infection with an adenovirus encoding YB-1 (AdYB-1), prevented hypertrophic growth under α-adrenergic stimulation with phenylephrine (PE), but not under stimulation with growth differentiation factor 15 (GDF15; n = 10–16). An adenovirus encoding the green fluorescent protein (AdGFP) served as the control. YB-1 overexpression enhanced the mRNA expression of the Gq inhibitor regulator of G-protein signaling 2 (RGS2) under PE stimulation (n = 6), potentially explaining its inhibitory effect on PE-induced hypertrophic growth. This study shows that YB-1 protects cardiomyocytes against PE-induced hypertrophic growth. Like in human end-stage heart failure, YB-1 downregulation may cause the heart to lose its protection against hypertrophic stimuli and progress to heart failure. Therefore, the transcription factor YB-1 is a pivotal signaling molecule, providing perspectives for therapeutic approaches. LA - English DB - MTMT ER - TY - JOUR AU - Vörös, Imre AU - Sághy, Éva AU - Pohóczky, Krisztina AU - Makkos, András AU - Onódi, Zsófia AU - Brenner, Gábor AU - Baranyai, Tamás AU - Ágg, Bence AU - Váradi, Barnabás AU - Kemény, Ágnes AU - Leszek, Przemyslaw AU - Görbe, Anikó AU - Varga, Zoltán AU - Giricz, Zoltán AU - Schulz, Rainer AU - Helyes, Zsuzsanna AU - Ferdinandy, Péter TI - Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection JF - FRONTIERS IN PHARMACOLOGY J2 - FRONT PHARMACOL VL - 12 PY - 2021 PG - 15 SN - 1663-9812 DO - 10.3389/fphar.2021.663655 UR - https://m2.mtmt.hu/api/publication/32506486 ID - 32506486 N1 - * Megosztott szerzőség LA - English DB - MTMT ER - TY - JOUR AU - Onódi, Zsófia AU - Ruppert, Mihály AU - Kucsera, Dániel AU - Sayour, Alex Ali AU - Tóth, Viktória AU - Koncsos, Gábor AU - Novák, Julianna AU - Brenner, Gábor AU - Makkos, András AU - Baranyai, Tamás AU - Giricz, Zoltán AU - Görbe, Anikó AU - Leszek, Przemyslaw AU - Gyöngyösi, Mariann AU - Horváth, Iván AU - Schulz, Rainer AU - Merkely, Béla Péter AU - Ferdinandy, Péter AU - Radovits, Tamás AU - Varga, Zoltán TI - AIM2-driven inflammasome activation in heart failure JF - CARDIOVASCULAR RESEARCH J2 - CARDIOVASC RES VL - 117 PY - 2021 IS - 13 SP - 2639 EP - 2651 PG - 13 SN - 0008-6363 DO - 10.1093/cvr/cvab202 UR - https://m2.mtmt.hu/api/publication/32068433 ID - 32068433 N1 - * Megosztott szerzőség LA - English DB - MTMT ER - TY - JOUR AU - Brenner, Gábor AU - Giricz, Zoltán AU - Garamvölgyi, Rita AU - Makkos, András AU - Onódi, Zsófia AU - Sayour, Viktor Nabil AU - Gergely, Tamás G AU - Baranyai, Tamás AU - Petneházy, Örs AU - Kőrösi, Dénes AU - Szabó, P. Gergő AU - Vágó, Hajnalka AU - Dohy, Zsófia AU - Czimbalmos, Csilla AU - Merkely, Béla Péter AU - Boldin-Adamsky, Swetlana AU - Feinstein, Elena AU - Horváth, Iván AU - Ferdinandy, Péter TI - Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs JF - JOVE-JOURNAL OF VISUALIZED EXPERIMENTS J2 - JOVE-J VIS EXP VL - 2021 PY - 2021 IS - 170 PG - 25 SN - 1940-087X DO - 10.3791/61901 UR - https://m2.mtmt.hu/api/publication/31992276 ID - 31992276 N1 - * Megosztott szerzőség LA - English DB - MTMT ER - TY - JOUR AU - Brenner, Gábor AU - Makkos, András AU - Nagy, Csilla Terézia AU - Onódi, Zsófia AU - Sayour, Viktor Nabil AU - Gergely, Tamás G AU - Kiss, Bernadett AU - Görbe, Anikó AU - Sághy, Éva AU - Zádori, Zoltán Sándor AU - Lázár, Bernadette AU - Baranyai, Tamás AU - Varga, Richárd Sándor AU - Husti, Zoltán AU - Varró, András AU - Tóthfalusi, László AU - Schulz, Rainer AU - Baczkó, István AU - Giricz, Zoltán AU - Ferdinandy, Péter TI - Hidden Cardiotoxicity of Rofecoxib Can be Revealed in Experimental Models of Ischemia/Reperfusion JF - CELLS J2 - CELLS-BASEL VL - 9 PY - 2020 IS - 3 PG - 17 SN - 2073-4409 DO - 10.3390/cells9030551 UR - https://m2.mtmt.hu/api/publication/31203017 ID - 31203017 N1 - * Megosztott szerzőség AB - Cardiac adverse effects are among the leading causes of the discontinuation of clinical trials and the withdrawal of drugs from the market. The novel concept of 'hidden cardiotoxicity' is defined as cardiotoxicity of a drug that manifests in the diseased (e.g. ischemic/reperfused), but not in the healthy heart or as a drug-induced deterioration of cardiac stress adaptation (e.g. ischemic conditioning). Here, we aimed to test if the cardiotoxicity of a selective COX-2 inhibitor rofecoxib that was revealed during its clinical use, i.e., increased occurrence of proarrhythmic and thrombotic events, could have been revealed in early phases of drug development by using preclinical models of ischemia/reperfusion (I/R) injury. Rats that were treated with rofecoxib or vehicle for four weeks were subjected to 30 min. coronary artery occlusion and 120 min. reperfusion with or without cardioprotection that is induced by ischemic preconditioning (IPC). Rofecoxib increased overall the arrhythmias including ventricular fibrillation (VF) during I/R. The proarrhythmic effect of rofecoxib during I/R was not observed in the IPC group. Rofecoxib prolonged the action potential duration (APD) in isolated papillary muscles, which was not seen in the simulated IPC group. Interestingly, while showing hidden cardiotoxicity manifested as a proarrhythmic effect during I/R, rofecoxib decreased the infarct size and increased the survival of adult rat cardiac myocytes that were subjected to simulated I/R injury. This is the first demonstration that rofecoxib increased acute mortality due to its proarrhythmic effect via increased APD during I/R. Rofecoxib did not interfere with the cardiprotective effect of IPC; moreover, IPC was able to protect against rofecoxib-induced hidden cardiotoxicity. These results show that cardiac safety testing with simple preclinical models of I/R injury uncovers hidden cardiotoxicity of rofecoxib and might reveal the hidden cardiotoxicity of other drugs. LA - English DB - MTMT ER - TY - JOUR AU - Bukosza, Éva Nóra AU - Kaucsár, Tamás AU - Godó, Mária AU - Lajtár, Enikő AU - Tod, Pál AU - Koncsos, Gábor AU - Varga, Zoltán AU - Baranyai, Tamás AU - Nguyen, Minh Tu AU - Schachner, Helga AU - Sőti, Csaba AU - Ferdinandy, Péter AU - Giricz, Zoltán AU - Szénási, Gábor AU - Hamar, Péter TI - Glomerular Collagen Deposition and Lipocalin-2 Expression Are Early Signs of Renal Injury in Prediabetic Obese Rats JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 20 PY - 2019 IS - 17 PG - 17 SN - 1661-6596 DO - 10.3390/ijms20174266 UR - https://m2.mtmt.hu/api/publication/30789521 ID - 30789521 N1 - * Megosztott szerzőség AB - Feeding rats with high-fat diet (HFD) with a single streptozotocin (STZ) injection induced obesity, slightly elevated fasting blood glucose and impaired glucose and insulin tolerance, and caused cardiac hypertrophy and mild diastolic dysfunction as published before by Koncsos et al. in 2016. Here we aimed to explore the renal consequences in the same groups of rats. Male Long-Evans rats were fed normal chow (CON; n = 9) or HFD containing 40% lard and were administered STZ at 20 mg/kg (i.p.) at week four (prediabetic rats, PRED, n = 9). At week 21 blood and urine samples were taken and kidney and liver samples were collected for histology, immunohistochemistry and for analysis of gene expression. HFD and STZ increased body weight and visceral adiposity and plasma leptin concentration. Despite hyperleptinemia, plasma C-reactive protein concentration decreased in PRED rats. Immunohistochemistry revealed elevated collagen IV protein expression in the glomeruli, and Lcn2 mRNA expression increased, while Il-1β mRNA expression decreased in both the renal cortex and medulla in PRED vs. CON rats. Kidney histology, urinary protein excretion, plasma creatinine, glomerular Feret diameter, desmin protein expression, and cortical and medullary mRNA expression of TGF-β1, Nrf2, and PPARγ were similar in CON and PRED rats. Reduced AMPKα phosphorylation of the autophagy regulator Akt was the first sign of liver damage, while plasma lipid and liver enzyme concentrations were similar. In conclusion, glomerular collagen deposition and increased lipocalin-2 expression were the early signs of kidney injury, while most biomarkers of inflammation, oxidative stress and fibrosis were negative in the kidneys of obese, prediabetic rats with mild heart and liver injury. LA - English DB - MTMT ER - TY - JOUR AU - Lukovic, Dominika AU - Gugerell, Alfred AU - Zlabinger, Katrin AU - Winkler, Johannes AU - Pavo, Noemi AU - Baranyai, Tamás AU - Giricz, Zoltán AU - Varga, Zoltán AU - Riesenhuber, Martin AU - Spannbauer, Andreas AU - Traxler, Denise AU - Jakab, András AU - Garamvölgyi, Rita AU - Petneházy, Örs AU - Pils, Dietmar AU - Tóth, Levente AU - Schulz, Rainer AU - Ferdinandy, Péter AU - Gyöngyösi, Mariann TI - Transcriptional Alterations by Ischaemic Postconditioning in a Pig Infarction Model: Impact on Microvascular Protection JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 20 PY - 2019 IS - 2 PG - 19 SN - 1661-6596 DO - 10.3390/ijms20020344 UR - https://m2.mtmt.hu/api/publication/30403335 ID - 30403335 LA - English DB - MTMT ER - TY - JOUR AU - Koncsos, Gábor AU - Varga, Zoltán AU - Baranyai, Tamás AU - Ferdinandy, Péter AU - Schulz, R. AU - Giricz, Zoltán AU - Boengler, K. TI - Nagarse treatment of cardiac subsarcolemmal and interfibrillar mitochondria accounts for inaccurate quantification of proteins JF - JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY J2 - J MOL CELL CARDIOL VL - 120 PY - 2018 IS - Suppl. S SP - 5 EP - 6 PG - 3 SN - 0022-2828 DO - 10.1016/j.yjmcc.2018.05.029 UR - https://m2.mtmt.hu/api/publication/32110245 ID - 32110245 LA - English DB - MTMT ER - TY - THES AU - Baranyai, Tamás TI - REMOTE ISCHEMIC CONDITIONING AND ITS MOLECULAR MECHANISM IN THE HEART PB - Semmelweis Egyetem PY - 2018 DO - 10.14753/SE.2018.2082 UR - https://m2.mtmt.hu/api/publication/3419044 ID - 3419044 LA - English DB - MTMT ER - TY - JOUR AU - Ágg, Bence AU - Baranyai, Tamás AU - Makkos, András AU - Veto, B AU - Faragó, Nóra AU - Zvara, Ágnes AU - Giricz, Zoltán AU - Veres, Dániel AU - Csermely, Péter AU - Arányi, Tamás AU - Puskás, László AU - Varga, Zoltán AU - Ferdinandy, Péter TI - Author Correction: MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 8 PY - 2018 IS - 1 PG - 1 SN - 2045-2322 DO - 10.1038/s41598-018-30163-9 UR - https://m2.mtmt.hu/api/publication/3407315 ID - 3407315 LA - English DB - MTMT ER -