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Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Research, Development and Innovation Office of Hungary (NKFIA; NVKP-16-1-2016-0017 National Heart Program and OTKA-FK 134751); MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary We have previously identified several cardiac microRNAs that are involved in cardioprotection and termed them as ProtectomiRs. mRNA targets of these ProtectomiRs may reveal new drug targets for cardioprotection. Here we aimed to identify key molecular targets of ProtectomiRs and confirm their association with cardioprotection in a translational pig model of acute myocardial infarction. Network theoretical approach was utilized to identify 882 potential target genes of 18 previously described protectomiRs. Rictor gene was the most central and it was ranked first in the protectomiR-target mRNA molecular network with the highest node degree of 5. Therefore, expression of Rictor and its targeting microRNAs were further validated in heart samples obtained from a translational pig model of acute myocardial infarction and cardioprotection induced by pre- or postconditioning. Three out of five Rictor-targeting pig homologue of rat ProtectomiRs showed significant upregulation in postconditioned but not in preconditioned pig hearts. Rictor was downregulated at the mRNA and protein level in ischemic postconditioning but not in ischemic preconditioning. This is the first demonstration that Rictor is the central molecular target of ProtectomiRs and that decreased Rictor expression may regulate ischemic postconditioning-, but not preconditioning-induced acute cardioprotection. We conclude that Rictor is a potential novel drug target for acute cardioprotection. [ABSTRACT FROM AUTHOR]

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by the National Research, Development and Innovation Office of Hungary (NKFIA; NVKP-16-1-2016-0017 National Heart Program) and the Thematic Excellence Programme (2020-4.1.1.-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development and Molecular Biology thematic programmes of the Semmelweis University. Introduction There is a growing body of evidence that changes in cardiac microRNA expression pattern plays an important role in cardioprotective cellular signaling. Purpose Our aim was to identify evolutionarily conserved cardioprotective microRNA (protectomiR) families with a high probability of translation into human clinical practice. Methods Global cardiac microRNA expression profiles were measured in both a rat and a porcine model of myocardial infarction with or without ischemic preconditioning and postconditioning by microarray and high-throughput polymerase chain reaction, respectively. A software developed by our team was used to identify cross-species microRNA families (i.e. microRNAs with identic seed sequence) with cardioprotective expression patterns. By selecting experimentally validated human target genes from the miRTarBase database we built a microRNA family-target interaction network by the miRNAtarget.com software. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the selected target genes. Results Due to potential patenting, microRNAs and microRNA families were anonymized. We identified 7 microRNA families, showing cardioprotective expression pattern. Based on the analysis of the microRNA family-target network, expression change of the target hubs were predicted to be consistent with previously described changes in pathways with high relevance in cardioprotection (e.g. positive regulation of TGF-beta, HIF-1, PI3K-Akt signaling pathways). Conclusion By an unbiased transcriptomics and bioinformatics based approach we successfully identified microRNA families with robust cross-species protectomiR expression pattern and targets involved in well-established cardioprotective pathways. These cardioprotective microRNA families are of high translational value for human clinical application. [ABSTRACT FROM AUTHOR]

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., (© 2023. The Author(s).)

Unlabelled: There are only very few epidemiological data about homocysteine levels in patients suffering from cardiovascular (CV) disease in Hungary, however, homocysteine is a newly recognized, independent risk factor of CV diseases., Aim of the Study: Therefore, in the present study, data of 1010 East-Hungarian patients with signs of CV disease were analyzed retrospectively for correlation between the level of homocysteine and CV diseases, laboratory parameters, as well as genetic differences., Patients and Methods: From the studied patient population a control ("healthy") group has been selected according to the following criteria: lack of previous stroke or stenosis of the carotid arteries or the lower extremities, lack of coronary artery stenosis more than 50%, no previous coronary intervention or an angiography diagnosed progression of the coronary atherosclerosis., Results: The level of homocysteine showed statistically significant negative linear correlation with HDL-cholesterol and the anti-atherogenic ApoAI, and showed a positive correlation with CRP and FXIII activities in the entire patient population. When compared to the control group, homocysteine level was significantly higher in patients with previous stroke or acute myocardial infarction, coronary stenosis, progressive coronary disease, physical inactivity, MTHFR gene polymorphism, low folate or vitamin B12 level in both men and women. In patients with type II diabetes the level of homocysteine was significantly higher only in women., Conclusions: It can be concluded that the level of homocysteine in patients suffering from various CV diseases is high in Hungary. This may have a prognostic value, and shows that reduction of homocysteine level in these patients may be beneficial.