Peter Ferdinandy

• MD, PhD, MBA
• Managing Director at Semmelweis University

Background Incretin analogues, used for the treatment of type 2 diabetes mellitus and obesity, such as GLP1-receptor agonist liraglutide (Lira) have been shown to reduce major adverse cardiac events in recent clinical trials of heart failure. Tirzepatide (TZP), a dual GIP/GLP1-receptor agonist has shown promising results in the SUMMIT trial as impr...

Post-marketing surveillance is crucial for drug safety, yet the tools of pharmacovigilance rely solely on text-based data that may limit the applicability of contemporary machine learning methodologies. Here, we adapt contrastive learning algorithms to generate adverse event vector representations from spontaneous reports to serve as general machin...

Background Diabetic cardiomyopathy (DCM) is a complex condition linked to diabetes, characterized by cardiac and vascular dysfunction, frequently concomitant with heart failure with preserved ejection fraction. The extracellular matrix glycoprotein Tenascin-C (TNC) has been found to be upregulated under diabetic conditions. However, the potential c...

Background Type 2 diabetes mellitus (T2DM) represents a significant risk factor for cardiovascular disease, particularly heart failure with preserved ejection fraction (HFpEF). HFpEF predominantly affects elderly individuals and women, and is characterized by dysfunctions associated with metabolic, inflammatory, and oxidative stress pathways. Despi...

Background Patients diagnosed with both aortic stenosis (AS) and diabetes mellitus (DM) encounter a distinctive set of challenges due to the interplay between these two conditions. This study aimed to investigate the effects of DM on the left ventricle in AS patients, specifically focusing on the inflammatory response, oxidative stress, and their i...

Background and Purpose Immune checkpoint inhibitors, such as anti­PD1, revolutionized melanoma treatment. However, resistance and low response rates remain problems. Our goal was to pinpoint actionable biomarkers of resistance to anti‐PD1 treatment and verify therapeutic effectiveness in vivo. Experimental Approach Using receiver operating charact...

Background/Objectives: Small cell lung cancer (SCLC) is one of the malignancies with the worst prognosis, and there have been no major breakthroughs in its treatment for a long time. The majority of patients are diagnosed at the extensive stage, where the only option is chemotherapy, and even the addition of immune checkpoint inhibitors results in...

Blood collection in mice is a common procedure in biomedical research. The choice of blood collection method and the need for analgesia and/or anaesthesia depend on multiple factors, including the experimental setup, animal welfare considerations and the intended downstream analyses. This minireview describes key non‐surgical and surgical blood col...

Although many cardioprotective interventions have been shown to limit infarct size (IS), in preclinical animal studies of acute myocardial ischemia/reperfusion injury (IRI), their clinical translation to patient benefit has been largely disappointing. A major factor is the lack of rigor and reproducibility in the preclinical studies. To address thi...

Despite substantial advances in cardiovascular pharmacotherapy and devices in recent years, prevention and treatment of many cardiovascular diseases (CVD) remain limited, thus reflecting the need for more effective and safer pharmacological strategies. In this review, we summarize the most relevant studies in cardiovascular pharmacotherapy in 2024,...

Background The flipped classroom (FC) approach has demonstrated efficacy in enhancing the learning process, including within higher education contexts such as medical education. Recently, FC has emerged as potential alternative to traditional teaching models across various disciplines, particularly due to its more engaging nature. However, there is...

In the past year, the European Medicines Agency (EMA), the Food and Drug Administration (FDA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) authorised 53 novel drugs. While the 2024 harvest is not as rich as in 2023, when 70 new chemical entities were approved, the number of ‘orphan’ drug authorisations in 2024 (21) is similar...

Background and Objective: Safety signals for potential drug-induced adverse events (AEs) typically emerge from multiple data sources, primarily spontaneous reporting systems (SRS), despite known limitations. Increasingly, real-world data (RWD) from sources like electronic health records (EHRs) and administrative databases are leveraged for signal d...

Introduction/Background: Cardiovascular symptoms appear in a high proportion of patients in the few months following a severe SARS-CoV-2 infection. Non-invasive methods to predict disease severity could help personalizing healthcare and reducing the occurrence of these symptoms. Research Questions/Hypothesis: We hypothesized that blood long noncodi...

Introduction: Immune checkpoint inhibitors (ICI), such as anti-PD-1 monoclonal antibodies are increasingly used in anti-cancer therapy. However, several cardiovascular adverse effects can occur with the use of ICIs, including new-onset heart failure. Hypothesis: We hypothesized that prior myocardial ischemic injury could exacerbate cardiac dysfunct...

Despite accumulating data on underlying mechanisms, the influence of sex and prevalent cardio-metabolic co-morbidities on the manifestation and severity of immune checkpoint inhibitor (ICI)-induced cardiotoxicity has not been well defined. To elucidate whether sex and prevalent cardio-metabolic co-morbidities affect ICI-induced cardiotoxicity, we r...

Background and purpose MicroRNA (miRNA) therapy is a promising approach to induce cardioprotection. We have previously identified cardiac microRNA‐125b* (microRNA‐125b‐2‐3p; miR‐125b*) as a potential cardioprotective miRNA, termed ProtectomiR. We aimed to characterize the pharmacokinetics and pharmacodynamics, and the effect of miR‐125b* mimic on i...

Aims The association and co-isolation of low-density lipoproteins (LDL) and extracellular vesicles (EVs) have been shown in blood plasma. Here we explore this relationship to better understand the role of EVs in atherogenesis. Methods and results Wild type (WT), PCSK9−/−, and LDLR−/− C57BL/6 mice were used in this study. Eleven week-old male mice...

In recent years, various approaches have been undertaken to eliminate lipoproteins co‐isolated with extracellular vesicles, as they were initially regarded as contaminating entities. However, novel discoveries are reshaping our perspective. In body fluids, these distinct particles not only co‐exist, but also interactions between them are likely to...

Three types of highly promising small RNA therapeutics, namely, small interfering RNAs (siRNAs), microRNAs (miRNAs) and the RNA subtype of antisense oligonucleotides (ASOs), offer advantages over small‐molecule drugs. These small RNAs can target any gene product, opening up new avenues of effective and safe therapeutic approaches for a wide range o...

Background and Purpose Cardioprotective miRNAs (protectomiRs) are promising therapeutic tools. Here, we aimed to identify protectomiRs in a translational porcine model of acute myocardial infarction (AMI) and to validate their cardiocytoprotective effect. Experimental Approach ProtectomiR candidates were selected after systematic analysis of miRNA...

Aims Heart failure with reduced ejection fraction (HFrEF) is a leading cause of death worldwide; thus, therapeutic improvements are needed. In vivo preclinical models are essential to identify molecular drug targets for future therapies. Transverse aortic constriction (TAC) is a well‐established model of HFrEF; however, highly experienced personnel...

Obesity and underweight are a growing health problem worldwide and a challenge for clinicians concerning antithrombotic therapy, due to the associated risks of thrombosis and/or bleeding. This clinical consensus statement updates a previous one published in 2018, by reviewing the most recent evidence on antithrombotic drugs based on body size categ...

In rats decreased bioavailability of nitric oxide induces oxidative stress and right heart failure. Oxidative stress can activate matrix metalloproteinase-2 (MMP2). We addressed the question whether increasing oxidative defense by administration of the SOD mimetic Tempol or direct inhibition of MMP2 activity by SB-3CT mitigates right heart failure....

Sodium glucose cotransporter 2 inhibitors (SGLT2i) constitute the only medication class that consistently prevents or attenuates human heart failure (HF) independent of ejection fraction. We have suggested earlier that the protective mechanisms of the SGLT2i Empagliflozin (EMPA) are mediated through reductions in the sodium hydrogen exchanger 1 (NH...

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by unleashing the power of the immune system against malignant cells. However, their use is associated with a spectrum of adverse effects, including cardiovascular complications, which can pose significant clinical challenges. Several mechanisms contribute to cardiovascular toxi...

Sodium–glucose cotransporter 2 inhibitors (SGLT2i), a new drug class initially designed and approved for treatment of diabetes mellitus, have been shown to exert pleiotropic metabolic and direct cardioprotective and nephroprotective effects that extend beyond their glucose-lowering action. These properties prompted their use in two frequently inter...

Mitochondria are the energy-producing organelles of mammalian cells with critical involvement in metabolism and signaling. Studying their regulation in pathological conditions may lead to the discovery of novel drugs to treat, for instance, cardiovascular or neurological diseases, which affect high-energy-consuming cells such as cardiomyocytes, hep...

Introduction: Ischemic conditionings (ICon) were intensively investigated and several protective signaling pathways were identified. Previously, we have shown the role of matrix metalloproteinases (MMP) in myocardial ischemia/reperfusion injury (MIRI) and the cardioprotective role of biglycan (BGN), a small leucine-rich proteoglycan in vitro. Here,...

The immunotherapy revolution with the use of immune checkpoint inhibitors (ICIs) started with the clinical use of the first ICI, ipilimumab, in 2011. Since then, the field of ICI therapy has rapidly expanded — with the FDA approval of 10 different ICI drugs so far and their incorporation into the therapeutic regimens of a range of malignancies. Whi...

Hypercholesterolemia (HC) induces, propagates and exacerbates cardiovascular diseases via various mechanisms that are yet not properly understood. Extracellular vesicles (EVs) are involved in the pathomechanism of these diseases. To understand how circulating or cardiac-derived EVs could affect myocardial functions, we analyzed the metabolomic prof...

Tools for predicting COVID-19 outcomes enable personalized healthcare, potentially easing the disease burden. This collaborative study by 15 institutions across Europe aimed to develop a machine learning model for predicting the risk of in-hospital mortality post-SARS-CoV-2 infection. Blood samples and clinical data from 1286 COVID-19 patients coll...

Background Cardiac troponin I (cTnI) above the 99th percentile is associated with an increased risk of major adverse events. Patients with detectable cTnI below the 99th percentile are a heterogeneous group with a less well-defined risk profile. The purpose of this study is to investigate the prognostic relevance of detectable cTnI below the 99th p...

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...

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 H...

Purpose of Review Immune checkpoint inhibitor (ICI) therapy has emerged as a pivotal advancement in cancer treatment, but the widespread adoption has given rise to a growing number of reports detailing significant cardiovascular toxicity. This review concentrates on elucidating the mechanisms behind ICI-related cardiovascular complications, emphasi...

Immune checkpoint molecules are physiological regulators of the adaptive immune response. Immune checkpoint inhibitors (ICIs), such as monoclonal antibodies targeting programmed cell death protein 1 or cytotoxic T lymphocyte-associated protein 4, have revolutionized cancer treatment and their clinical use is increasing. However, ICIs can cause vari...

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 whethe...

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...

Background and Purpose To protect against SARS‐CoV‐2 infection, the first mRNA‐based vaccines, Spikevax (mRNA‐1273, Moderna) and Comirnaty (BNT162b2, Pfizer/Biontech), were approved in 2020. The structure and assembly of the immunogen—in both cases, the SARS‐CoV‐2 spike (S) glycoprotein—are determined by a messenger RNA sequence that is translated...

The present review summarizes the beneficial and detrimental roles of reactive oxygen species in myocardial ischemia/reperfusion injury and cardioprotection. In the first part, the continued need for cardioprotection beyond that by rapid reperfusion of acute myocardial infarction is emphasized. Then, pathomechanisms of myocardial ischemia/reperfusi...

Although systolic function characteristically shows gradual impairment in pressure overload (PO)-evoked left ventricular (LV) hypertrophy (LVH), rapid progression to congestive heart failure (HF) occurs in distinct cases. The molecular mechanisms for the differences in maladaptation are unknown. Here, we examined microRNA (miRNA) expression and miR...

The identification of novel drug targets is needed to improve the outcomes of heart failure (HF). G-protein-coupled receptors (GPCRs) represent the largest family of targets for already approved drugs, thus providing an opportunity for drug repurposing. Here, we aimed (i) to investigate the differential expressions of 288 cardiac GPCRs via droplet...

With the improvement in cancer prognosis due to advances in antitumor therapeutic protocols and new targeted and immunotherapies, we are witnessing a growing increase in survival, however, at the same timeincrease in morbidity among cancer survivors as a consequences of the increased cardiovascular adverse effects of antineoplastic drugs. Common ca...

Background: Uveal melanoma is a poor prognosis cancer. Ergolide, a sesquiterpene lactone isolated from Inula Brittanica , exerts anti-cancer properties. The objective of this study was to 1) evaluate whether ergolide reduced metastatic uveal melanoma (MUM) cell survival/viability in vitro and in vivo ; and 2) to understand the molecular mechanism o...

Duchenne muscular dystrophy (DMD) is characterized by wasting of muscles that leads to difficulty moving and premature death, mainly from heart failure. Glucocorticoids are applied in the management of the disease, supporting the hypothesis that inflammation may be driver as well as target. However, the inflammatory mechanisms during progression of...

The cardiomyocyte-specific knockout (KO) of monoamine oxidase (MAO)-B, an enzyme involved in the formation of reactive oxygen species (ROS), reduced myocardial ischemia/reperfusion (I/R) injury in vitro. Because sex hormones have a strong impact on MAO metabolic pathways, we analyzed the myocardial infarct size (IS) following I/R in female and male...

Comprehensive understanding of the human protein-protein interaction (PPI) network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Despite the remarkable experimental efforts undertaken to date to determine the structure of the human interactome, many PPIs remain...

Open in new tabDownload slide Schematic diagram listing the established confounders of cardioprotection and characterizing in more detail the features of the novel confounder ‘primordial non-responsiveness to cardioprotection’, as evidenced by lack of protection (reduced arrhythmias, contractile dysfunction, infarct size, and coronary microvascula...

Aims: Remote ischemic preconditioning (RIPC) is a robust cardioprotective intervention in preclinical studies. To establish a working and efficacious RIPC protocol in our laboratories, we performed randomized, blinded in vivo studies in three study centres in rats, with various RIPC protocols. To verify that our experimental settings are in good a...

Lipid-lowering drugs have been shown to have cardioprotective effects but may have hidden cardiotoxic properties. Therefore, here we aimed to investigate if chronic treatment with the novel lipid-lowering drug bempedoic acid (BA) exerts hidden cardiotoxic and/or cardioprotective effects in a rat model of acute myocardial infarction (AMI). Wistar ra...

Interleukin-1β (IL-1β) is a key mediator of non-alcoholic steatohepatitis (NASH), a chronic liver disease, and of systemic inflammation-driven aging. IL-1β contributes to cardio-metabolic decline, and may promote hepatic oncogenic transformation. Therefore, IL-1β is a potential therapeutic target in these pathologies. We aimed to investigate the he...

The available pharmacological options in the management of cardiovascular diseases such as ischaemic heart disease and subsequent heart failure are effective in slowing the progression of this condition. However, the long‐term prognosis is still poor, raising the demand for new therapeutic strategies. Drug repurposing is a time‐ and cost‐effective...

Background and Purpose Immune checkpoint inhibitors (ICI), such as anti‐PD‐1 monoclonal antibodies, have revolutionized cancer therapy by enhancing the cytotoxic effects of T‐cells against tumours. However, enhanced T‐cell activity also may cause myocarditis and cardiotoxicity. Our understanding of the mechanisms of ICI‐induced cardiotoxicity is li...

Myocardial protection against ischemia/reperfusion injury (IRI) is mediated by various ligands, activating different cellular signaling cascades. These include classical cytosolic mediators such as cyclic-GMP (c-GMP), various kinases such as Phosphatydilinositol-3- (PI3K), Protein Kinase B (Akt), Mitogen-Activated-Protein- (MAPK) and AMP-activated...

Volume-induced hypertrophy is one of the risk factors for cardiac morbidity and mortality. In addition, mechanical and metabolic dysfunction, aging, and cellular redox balance are also contributing factors to the disease progression. In this study, we used volume overload (VO), which was induced by an aortocaval fistula in 2-month-old male Wistar r...

IntroductionSignal detection yields confirmed signals in only 2.1%, which imposes a heavy burden on the pharmacovigilance system in the European Union.Objectives We aimed to develop a network theoretical metric to increase the confirmed signal ratio of individual case safety report (ICSR) networks.MethodsICSRs of five cardiovascular adverse events...

Background Migraine is a primary headache with genetic susceptibility, but the pathophysiological mechanisms are poorly understood, and it remains an unmet medical need. Earlier we demonstrated significant differences in the transcriptome of migraineurs' PBMCs (peripheral blood mononuclear cells), suggesting the role of neuroinflammation and mitoch...

Clinical observations are highly inconsistent with the use of the antidiabetic rosiglitazone regarding its associated increased risk of myocardial infarction. This may be due to its hidden cardiotoxic properties that have only become evident during post-marketing studies. Therefore, we aimed to investigate the hidden cardiotoxicity of rosiglitazone...

Long COVID has become a world-wide, non-communicable epidemic, caused by long-lasting multi-organ symptoms that endure for weeks or months after SARS-CoV-2 infection has already subsided. This scientific document aims to provide insight into the possible causes and therapeutic options available for the cardiovascular manifestations of long COVID. I...

Dipeptidyl-peptidase-4 (DPP4) inhibitors are novel medicines for diabetes. The SAVOR-TIMI-53 clinical trial revealed increased heart-failure-associated hospitalization in saxagliptin-treated patients. Although this side effect could limit therapeutic use, the mechanism of this potential cardiotoxicity is unclear. We aimed to establish a cellular pl...

Vascular smooth muscle cells (SMC) possess a unique cytoplasticity, regulated by transcriptional, translational and phenotypic transformation in response to a diverse range of extrinsic and intrinsic pathogenic factors. The mature, differentiated SMC phenotype is physiologically typified transcriptionally by expression of genes encoding “contractil...

Hypoxia upregulates PCSK9 expression in the heart, and PCSK9 affects the function of myocytes. This study aimed to investigate the impact of PCSK9 on reperfusion injury in rats and mice fed normal or high-fat diets. Either the genetic knockout of PCSK9 (mice) or the antagonism of circulating PCSK9 via Pep2-8 (mice and rats) was used. Isolated perfu...

Aims: Inflammatory pathways are increasingly recognized as an important factor in the pathophysiology of both heart failure (HF) and atrial fibrillation (AF). However, there is no data about inflammation-related histological and molecular alterations in HF-associated AF. The objective of our study was to investigate inflammatory pathways and fibro...

Aims: Volume overload (VO) induced hypertrophy is one of the hallmarks to the development of heart diseases. Understanding the compensatory mechanisms involved in this process might help preventing the disease progression. Methods and results: Therefore, the present study used 2 months old Wistar rats, which underwent an aortocaval fistula to de...

Objectives: Cold ischemia and subsequent reperfusion injury are non-immunologic cornerstones in the development of graft injury after heart transplantation. The nitric oxide donor S-nitroso-human-serum-albumin (S-NO-HSA) is known to attenuate myocardial ischemia-reperfusion (I/R)-injury. We assessed whether donor preservation with S-NO-HSA affects...

Background Cardiac cell lines and primary cells are widely used in cardiovascular research. Despite increasing number of publications using these models, comparative characterization of these cell lines has not been performed, therefore, their limitations are undetermined. We aimed to compare cardiac cell lines to primary cardiomyocytes and to matu...

Pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) is a multifunctional neuropeptide, which may play a role in cardioprotection. However, little is known about the presence of PACAP-38 in heart failure (HF) patients. The aim of our study was to measure the alterations of PACAP-38 like immunoreactivity (LI) in acute (n = 13) and chroni...

Background The investigation of possible interactions between two proteins in intracellular signaling is an expensive and laborious procedure in the wet-lab, therefore, several in silico approaches have been implemented to narrow down the candidates for future experimental validations. Reformulating the problem in the field of network theory, the s...

The release of extracellular vesicles (EVs) is increased under cellular stress and cardiomyocyte damaging conditions. However, whether the cardiomyocyte-derived EVs eventually reach the systemic circulation and whether their number in the bloodstream reflects cardiac injury, remains unknown. Wild type C57B/6 and conditional transgenic mice expressi...