TY - JOUR AU - Kucsera, Dániel AU - Ruppert, Mihály AU - Sayour, Viktor Nabil AU - Tóth, Viktória AU - Kovács, Tamás AU - Hegedűs, Zsombor AU - Onódi, Zsófia AU - Fábián, Alexandra AU - Kovács, Attila AU - Radovits, Tamás AU - Merkely, Béla Péter AU - Pacher, Pál AU - Ferdinandy, Péter AU - Varga, Zoltán TI - NASH triggers cardiometabolic HFpEF in aging mice JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - In press PY - 2024 SN - 2509-2715 DO - 10.1007/s11357-024-01153-9 UR - https://m2.mtmt.hu/api/publication/34799327 ID - 34799327 AB - Both heart failure with preserved ejection fraction (HFpEF) and non-alcoholic fatty liver disease (NAFLD) develop due to metabolic dysregulation, has similar risk factors (e.g., insulin resistance, systemic inflammation) and are unresolved clinical challenges. Therefore, the potential link between the two disease is important to study. We aimed to evaluate whether NASH is an independent factor of cardiac dysfunction and to investigate the age dependent effects of NASH on cardiac function. C57Bl/6 J middle aged (10 months old) and aged mice (24 months old) were fed either control or choline deficient (CDAA) diet for 8 weeks. Before termination, echocardiography was performed. Upon termination, organ samples were isolated for histological and molecular analysis. CDAA diet led to the development of NASH in both age groups, without inducing weight gain, allowing to study the direct effect of NASH on cardiac function. Mice with NASH developed hepatomegaly, fibrosis, and inflammation. Aged animals had increased heart weight. Conventional echocardiography revealed normal systolic function in all cohorts, while increased left ventricular volumes in aged mice. Two-dimensional speckle tracking echocardiography showed subtle systolic and diastolic deterioration in aged mice with NASH. Histologic analyses of cardiac samples showed increased cross-sectional area, pronounced fibrosis and Col1a1 gene expression, and elevated intracardiac CD68 + macrophage count with increased Il1b expression. Conventional echocardiography failed to reveal subtle change in myocardial function; however, 2D speckle tracking echocardiography was able to identify diastolic deterioration. NASH had greater impact on aged animals resulting in cardiac hypertrophy, fibrosis, and inflammation. LA - English DB - MTMT ER - TY - JOUR AU - Papapetropoulos, Andreas AU - Topouzis, Stavros AU - Alexander, Steve P. H. AU - Cortese‐Krott, Miriam AU - Kendall, Dave A. AU - Martemyanov, Kirill A. AU - Mauro, Claudio AU - Nagercoil, Nithyanandan AU - Panettieri, Reynold A. AU - Patel, Hemal H. AU - Schulz, Rainer AU - Stefanska, Barbara AU - Stephens, Gary J. AU - Teixeira, Mauro M. AU - Vergnolle, Nathalie AU - Wang, Xin AU - Ferdinandy, Péter TI - Novel drugs approved by the EMA, the FDA, and the MHRA in 2023: A year in review JF - BRITISH JOURNAL OF PHARMACOLOGY J2 - BR J PHARMACOL VL - In press PY - 2024 SN - 0007-1188 DO - 10.1111/bph.16337 UR - https://m2.mtmt.hu/api/publication/34753997 ID - 34753997 AB - In 2023, seventy novel drugs received market authorization for the first time in either Europe (by the EMA and the MHRA) or in the United States (by the FDA). Confirming a steady recent trend, more than half of these drugs target rare diseases or intractable forms of cancer. Thirty drugs are categorized as “first‐in‐class” (FIC), illustrating the quality of research and innovation that drives new chemical entity discovery and development. We succinctly describe the mechanism of action of most of these FIC drugs and discuss the therapeutic areas covered, as well as the chemical category to which these drugs belong. The 2023 novel drug list also demonstrates an unabated emphasis on polypeptides (recombinant proteins and antibodies), Advanced Therapy Medicinal Products (gene and cell therapies) and RNA therapeutics, including the first‐ever approval of a CRISPR‐Cas9‐based gene‐editing cell therapy. LA - English DB - MTMT ER - TY - JOUR AU - Sayour, Viktor Nabil AU - Paál, Ágnes AU - Ameri, Pietro AU - Meijers, Wouter C AU - Minotti, Giorgio AU - Andreadou, Ioanna AU - Lombardo, Antonella AU - Camilli, Massimiliano AU - Drexel, Heinz AU - Grove, Erik Lerkevang AU - Dan, Gheorghe Andrei AU - Ivanescu, Andreea AU - Semb, Anne Grete AU - Savarese, Gianluigi AU - Dobrev, Dobromir AU - Crea, Filippo AU - Kaski, Juan-Carlos AU - de Boer, Rudolf A AU - Ferdinandy, Péter AU - Varga, Zoltán TI - Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence JF - EUROPEAN HEART JOURNAL J2 - EUR HEART J VL - 45 PY - 2024 IS - 14 SP - 1224 EP - 1240 PG - 17 SN - 0195-668X DO - 10.1093/eurheartj/ehae105 UR - https://m2.mtmt.hu/api/publication/34724783 ID - 34724783 N1 - Cited By :2 Export Date: 14 April 2024 CODEN: EHJOD AB - Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided. LA - English DB - MTMT ER - TY - JOUR AU - Michel, Lars AU - Ferdinandy, Péter AU - Rassaf, Tienush TI - Cellular Alterations in Immune Checkpoint Inhibitor Therapy-Related Cardiac Dysfunction JF - CURRENT HEART FAILURE REPORTS J2 - CURR HEART FAIL REP PY - 2024 SN - 1546-9530 DO - 10.1007/s11897-024-00652-2 UR - https://m2.mtmt.hu/api/publication/34717730 ID - 34717730 LA - English DB - MTMT ER - TY - JOUR AU - Tamargo, Juan AU - Agewall, Stefan AU - Borghi, Claudio AU - Ceconi, Claudio AU - Cerbai, Elisabetta AU - Dan, Gheorghe A AU - Ferdinandy, Péter AU - Grove, Erik Lerkevang AU - Rocca, Bianca AU - Magavern, Emma AU - Sulzgruber, Patrick AU - Semb, Anne Grete AU - Sossalla, Samuel AU - Niessner, Alexander AU - Kaski, Juan Carlos AU - Dobrev, Dobromir TI - New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2023 JF - EUROPEAN HEART JOURNAL - CARDIOVASCULAR PHARMACOTHERAPY J2 - EUR HEART J-CARD PHA PY - 2024 SN - 2055-6837 DO - 10.1093/ehjcvp/pvae013 UR - https://m2.mtmt.hu/api/publication/34676111 ID - 34676111 AB - Although cardiovascular diseases are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic cardiovascular disease and heart failure. The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolemia, type 2 diabetes, obesity and heart failure, the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of cardiovascular diseases. LA - English DB - MTMT ER - TY - JOUR AU - Gergely, Tamás G AU - Drobni, Zsófia AU - Kallikourdis, Marinos AU - Zhu, Han AU - Meijers, Wouter C. AU - Neilan, Tomas G. AU - Rassaf, Tienush AU - Ferdinandy, Péter AU - Varga, Zoltán TI - Immune checkpoints in cardiac physiology and pathology: therapeutic targets for heart failure JF - NATURE REVIEWS CARDIOLOGY J2 - NAT REV CARDIOL PY - 2024 SN - 1759-5002 DO - 10.1038/s41569-023-00986-9 UR - https://m2.mtmt.hu/api/publication/34538456 ID - 34538456 N1 - Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary Heart and Vascular Center, Semmelweis University, Budapest, Hungary Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, MA, United States Department of Biomedical Sciences, Humanitas University, Milan, Italy Adaptive Immunity Lab, Humanitas Research Hospital IRCCS, Milan, Italy Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, CA, United States Erasmus MC, Cardiovascular Institute, Thorax Center, Department of Cardiology, Rotterdam, Netherlands Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center Essen, Medical Faculty, University Hospital Essen, Essen, Germany Pharmahungary Group, Szeged, Hungary Export Date: 25 April 2024 Correspondence Address: Varga, Z.V.; Department of Pharmacology and Pharmacotherapy, Hungary; email: varga.zoltan@semmelweis.hu LA - English DB - MTMT ER - 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 - Ungvári, Zoltán István AU - Tabák, Ádám AU - Ádány, Róza AU - Purebl, György AU - Kaposvári, Csilla AU - Fazekas-Pongor, Vince AU - Csípő, Tamás AU - Szarvas, Zsófia AU - Horváth, Krisztián AU - Mukli, Péter AU - Balog, Piroska AU - Bódizs, Róbert AU - Ujma, Przemyslaw Péter AU - Stauder, Adrienne AU - Belsky, Daniel W. AU - Kovács, Illés AU - Yabluchanskiy, Andriy AU - Maier, Andrea B. AU - Moizs, Mariann AU - Östlin, Piroska AU - Yon, Yongjie AU - Varga, Péter AU - Vokó, Zoltán AU - Papp, Magor Csongor AU - Takács, István AU - Vásárhelyi, Barna AU - Torzsa, Péter AU - Ferdinandy, Péter AU - Csiszar, Anna AU - Benyó, Zoltán AU - Szabó, Attila AU - Bednárikné Dörnyei, Gabriella AU - Kivimäki, Mika AU - Kellermayer, Miklós AU - Merkely, Béla Péter TI - The Semmelweis Study: a longitudinal occupational cohort study within the framework of the Semmelweis Caring University Model Program for supporting healthy aging JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - 46 PY - 2024 IS - 1 SP - 191 EP - 218 PG - 28 SN - 2509-2715 DO - 10.1007/s11357-023-01018-7 UR - https://m2.mtmt.hu/api/publication/34425939 ID - 34425939 N1 - International Training Program in Geroscience/Healthy Aging Program, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Department of Health Promotion Sciences, The Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Department of Public Health, Faculty of Medicine, Semmelweis University, Budapest, Hungary UCL Brain Sciences, University College London, London, United Kingdom Department of Internal Medicine and Oncology, Semmelweis University, Faculty of Medicine, Budapest, Hungary HUN-REN-UD Public Health Research Group, Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Institute of Behavioral Sciences, Faculty of Medicine, Semmelweis University, Budapest, Hungary Robert N. Butler Columbia Aging Center, Columbia University, New York, NY, United States Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, United States Department of Ophthalmology, Faculty of Medicine, Semmelweis University, Budapest, Hungary Department of Ophthalmology, Weill Cornell Medical College, New York City, NY, United States Department of Clinical Ophthalmology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Centre for Healthy Longevity, National University Health System, Singapore, Singapore Department of Human Movement Sciences, @AgeAmsterdam, Vrije Universiteit, Amsterdam Movement Sciences, Amsterdam, Netherlands Ministry of Interior of Hungary, Budapest, Hungary WHO Regional Office for Europe, Copenhagen, Denmark Clinical Center, Semmelweis University, Budapest, Hungary Center for Health Technology Assessment, Semmelweis University, Budapest, Hungary Department of Laboratory Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary Department of Family Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary Department of Translational Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary HUN-REN-SU Cerebrovascular and Neurocognitive Diseases Research Group, Budapest, Hungary First Department of Pediatrics, Faculty of Medicine, Semmelweis University, Budapest, Hungary HUN-REN-SU Pediatrics and Nephrology Research Group, Semmelweis University, Budapest, Hungary Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary Department of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Budapest, Hungary Heart and Vascular Center, Semmelweis University, Budapest, Hungary Cited By :1 Export Date: 29 February 2024 Correspondence Address: Ungvari, Z.; International Training Program in Geroscience/Healthy Aging Program, Hungary; email: Zoltan-Ungvari@ouhsc.edu Correspondence Address: Adany, R.; International Training Program in Geroscience/Healthy Aging Program, Hungary AB - The Semmelweis Study is a prospective occupational cohort study that seeks to enroll all employees of Semmelweis University (Budapest, Hungary) aged 25 years and older, with a population of 8866 people, 70.5% of whom are women. The study builds on the successful experiences of the Whitehall II study and aims to investigate the complex relationships between lifestyle, environmental, and occupational risk factors, and the development and progression of chronic age-associated diseases. An important goal of the Semmelweis Study is to identify groups of people who are aging unsuccessfully and therefore have an increased risk of developing age-associated diseases. To achieve this, the study takes a multidisciplinary approach, collecting economic, social, psychological, cognitive, health, and biological data. The Semmelweis Study comprises a baseline data collection with open healthcare data linkage, followed by repeated data collection waves every 5 years. Data are collected through computer-assisted self-completed questionnaires, followed by a physical health examination, physiological measurements, and the assessment of biomarkers. This article provides a comprehensive overview of the Semmelweis Study, including its origin, context, objectives, design, relevance, and expected contributions. LA - English DB - MTMT ER - TY - JOUR AU - Fodor, Eszter AU - Nagy, Regina Norma AU - Nógrádi, András AU - Toovey, Stephen AU - Kamal, Mohamed A. AU - Vadász, Péter AU - Bencsik, Péter AU - Görbe, Anikó AU - Ferdinandy, Péter TI - An Observational Study on the Pharmacokinetics of Oseltamivir in Lactating Influenza Patients JF - CLINICAL PHARMACOLOGY & THERAPEUTICS J2 - CLIN PHARMACOL THER VL - 115 PY - 2024 IS - 2 SP - 318 EP - 323 PG - 6 SN - 0009-9236 DO - 10.1002/cpt.3107 UR - https://m2.mtmt.hu/api/publication/34368153 ID - 34368153 AB - Influenza infection may lead to serious complications in the postpartum period, therefore, oseltamivir treatment in these patients and their breastfed infants is of great importance. However, the pharmacokinetics of oseltamivir in postpartum lactating women with acute influenza infection, and the consequent infant exposure to oseltamivir are still unknown, and these data would help in assessing risk and the need for dose adjustment in breastfed infants. LA - English DB - MTMT ER - TY - JOUR AU - Haj-Yehia, Elias AU - Mincu, Raluca I. AU - Korste, Sebastian AU - Lampe, Lena AU - Margraf, Simone M. AU - Michel, Lars AU - Mahabadi, Amir A. AU - Ferdinandy, Péter AU - Rassaf, Tienush AU - Totzeck, Matthias TI - High neutrophil-to-lymphocyte ratio is associated with cancer therapy-related cardiovascular toxicity in high-risk cancer patients under immune checkpoint inhibitor therapy JF - CLINICAL RESEARCH IN CARDIOLOGY J2 - CLIN RES CARDIOL VL - 113 PY - 2024 IS - 2 SP - 301 EP - 312 PG - 12 SN - 1861-0684 DO - 10.1007/s00392-023-02327-9 UR - https://m2.mtmt.hu/api/publication/34329430 ID - 34329430 N1 - Export Date: 14 January 2024 LA - English DB - MTMT ER -