Investigating immune-inflammatory mechanisms and their pharmacological relevance in cardiac diseases and comorbidities

Summary

Cardiovascular diseases, including chronic heart failure (HF), remain among the leading causes of mortality worldwide. While the role of inflammation in disease progression is well recognized, its clinical translation remains challenging. Previous trials have shown that targeted anti-inflammatory therapies, such as monoclonal antibodies against IL-1β, are only effective in specific patient subgroups, highlighting the need for more precise therapeutic strategies in HF treatment.

This research aims to provide a deeper understanding of immune-inflammatory mechanisms and their pharmacological relevance in cardiac diseases. We focus particularly on the role of hematological and immunological comorbidities, as well as the regulation of cGAS-STING and inflammasome pathways, which may be key contributors to chronic HF progression. Additionally, we assess the cardiovascular impact of ATP-binding cassette (ABC) transporter inhibition, as these proteins play a role in adapting to inflammatory environments by clearing toxic metabolites and are significant in drug interactions.

This study addresses three main research questions:

1. How do hematological and immunological comorbidities contribute to the progression of cardiac diseases and the establishment of an immune-inflammatory environment in the bone marrow, spleen, and thymus?
2. Can inflammasome and cGAS-STING pathways be selectively targeted pharmacologically to develop novel therapeutic approaches for heart failure and other inflammatory diseases?
3. Does ABC transporter inhibition improve heart failure outcomes, or does it increase cardiovascular risks instead?Résztvevő kiemeltebb kutatók, kollaborációs partnerek, egyetemek, cégek (max. 100 szó)

Applied methods and tools

Our work is structured into three projects corresponding to these research questions:

1. Investigation of immune-hematological comorbidities and cardiac damage: We perform detailed characterization (by histology, immunoblot, qRT-PCR, etc) of leukocyte subpopulations and their phenotypic changes in human and animal heart samples.
2. Identification and pharmacological evaluation of inflammasome inhibitors: We develop an advanced in vitro cell-based drug-screening platform combining imaging flow cytometry with molecular biology techniques, including enzyme activity assays, immunoblot, etc.
3. Cardiovascular safety assessment of ABC transporter inhibition: We analyze the effects of ABCG2 inhibition on the heart and assess drug interaction risks in preclinical models.

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Mission and benefits

Our findings may contribute to the development of novel, targeted immunomodulatory therapies for heart failure while helping to identify critical drug interactions affecting cardiovascular safety. The new drug-screening platform may facilitate the identification of anti-inflammatory compounds, promoting more effective and safer therapeutic strategies.

Our research could have clinical and industrial relevance: it aims to identify new drug targets in cardiovascular diseases and to clarify the mechanism of action of already approved drugs. These efforts are essential to improve patients’ life expectancy, which indirectly supports the healthcare system. A detailed knowledge of these mechanisms, combined with preclinical drug screening, will facilitate the reuse of previously licensed drugs, a time- and cost-effective strategy for drug development.