Publications by authors named "Tamas G Gergely"

Background: Cardiac remodelling, a crucial aspect of heart failure, is commonly investigated in preclinical models by quantifying cardiomyocyte cross-sectional area (CSA) and microvascular density (MVD) via histological methods, such as immunohistochemistry. To achieve this, optimized protocols are needed, and the species specificity is dependent on the antibody used. Lectin histochemistry offers several advantages compared to antibody-based immunohistochemistry, including as cost-effectiveness and cross-species applicability.

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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 randomized 17-month-old male and female mice to receive control diet (CON) or high-fat diet (HFD) + L-NAME-a well-established mouse model of cardio-metabolic co-morbidities-for 17 weeks (n = 5-7), and evaluated markers of T-cell function in the spleen. As expected, HFD + L-NAME significantly increased body- and heart weight, and serum cholesterol levels, and caused no systolic dysfunction, however, led to diastolic dysfunction, cardiomyocyte hypertrophy, and increased fibrosis only in males compared to corresponding CON.

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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.

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Article Synopsis
  • - The study aimed to create a simpler mouse model of heart failure with reduced ejection fraction (HFrEF) using angiotensin-II treatment, comparing it to the traditional TAC model, which requires more skilled surgery and longer monitoring time.
  • - Analysis included mortality rates, heart function, structural changes, and gene expression, with statistical comparisons made between the two models to understand their similarities and differences.
  • - Results showed that while both models exhibited declines in heart function, the Ang-II treatment resulted in less heart dilation and hypertrophy compared to the TAC model, yet their molecular changes were strongly correlated.
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Article Synopsis
  • * These side effects result from immune system dysregulation and inflammation that target heart tissues, possibly leading to serious conditions like heart failure and arrhythmias.
  • * Understanding these mechanisms is vital for better patient care, so monitoring for cardiovascular toxicity is essential, and using biomarkers could improve early diagnosis and treatment.
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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 profile of circulating EVs, and we performed an in-depth analysis of cardiomyocyte (CM)-derived EVs in HC.

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Article Synopsis
  • Immune checkpoint molecules regulate the immune system and have led to a new era of cancer treatment with immune checkpoint inhibitors (ICIs), which can sometimes cause serious heart-related side effects.
  • Among these side effects, acute fulminant myocarditis is well-studied, but other chronic issues like accelerated atherosclerosis and heart failure are emerging as significant concerns.
  • The dysfunction of immune checkpoint signaling may disrupt heart health, suggesting that modulating these pathways could potentially offer new therapeutic strategies for treating heart failure.
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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 digital PCR (ddPCR) and bulk RNA sequencing (RNAseq) in a rat model of left ventricular pressure-overload; (ii) to compare RNAseq findings with those of ddPCR; and (iii) to screen and test for novel, translatable GPCR drug targets in HF.

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Aims: Remote ischaemic 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 alignment with in vivo rat studies showing cardioprotection by limb RIPC, we performed a systematic review and meta-analysis.

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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 rats were orally treated with BA or its vehicle for 28 days, anesthetized and randomized to three different groups (vehicle + ischemia/reperfusion (I/R), BA + I/R, and positive control vehicle + ischemic preconditioning (IPC)) and subjected to cardiac 30 min ischemia and 120 min reperfusion.

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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.

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Article Synopsis
  • - Immune checkpoint inhibitors, particularly anti-PD-1 monoclonal antibodies, can enhance T-cell activity against cancer but may also cause heart issues like myocarditis and cardiotoxicity, prompting research into their effects on cardiac function.
  • - In experiments using mice, anti-PD-1 treatment led to cardiac dysfunction and increased inflammation in the thymus, particularly with heightened IL-17A levels, while other inflammatory markers remained mild.
  • - Notably, blocking IL-17A prevented the cardiac dysfunction associated with PD-1 inhibition, suggesting that targeting IL-17A could mitigate the heart-related side effects of immune checkpoint therapy in cancer treatment.
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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 in ischemia/reperfusion (I/R) injury models.

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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.

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Article Synopsis
  • Cardiac cell lines (H9C2, AC16, HL-1) were systematically compared to primary cardiomyocytes and mature cardiac tissues to assess their characteristics and limitations in cardiovascular research.
  • Findings revealed that cardiac cell lines exhibited significantly lower expression of cardiac markers and less pronounced cardiac phenotypes compared to primary and mature cells, even after differentiation.
  • The study concludes that the low resemblance of cell lines to mature cardiac tissue limits their usefulness in research, highlighting the need to consider their translational value when selecting models for cardiomyocyte studies.
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The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an unmet clinical need for prevention and therapy of post-myocardial infarction heart failure (post-MI HF). Clinically relevant pig models of post-MI HF are prerequisites for final proof-of-concept studies before entering into clinical trials in drug and medical device development.

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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.

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