The Impact of pneumonia on the development of heart failure

• Applicant: Professor Dr. Arash Haghikia
• Subject Area: Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560579254

Community-acquired pneumonia (CAP) is one of the most common infectious diseases in industrialized countries and a leading cause of morbidity and mortality worldwide. Over the past two decades, substantial evidence has emerged showing that CAP can affect the cardiovascular system and contribute to the development or progression of cardiovascular diseases. In particular, CAP significantly increases the risk of future heart failure. Notably, the presence of certain comorbidities, especially hypertension, significantly contributes to the elevated risk of heart failure in pneumonia patients. These findings underscore the importance of clinical vigilance and timely recognition of cardiovascular diseases following CAP, and emphasize the need for a deeper understanding of the underlying pathomechanisms to develop novel therapeutic approaches and improve the prevention of pneumonia-induced heart failure. Although some dysregulations in cardiac physiology following pneumonia have been reported in clinical studies, the specific molecular pathways underlying the increased risk of heart failure remain largely unknown. In this project, we aim to investigate the adverse effects of pneumonia on cardiac function in more detail and to identify pathways that may be targeted for therapeutic purposes to protect the myocardium from pneumonia-induced damage. For our studies, we will use a mouse model in which pneumonia is induced by transnasal inoculation of S. pneumoniae, followed by antibiotic treatment with ampicillin after a 60-hour delay. This protocol induces multifocal necrotizing pneumonia with significant perivascular edema and early-stage leukocyte infiltration, which diminishes after the initiation of antibiotic treatment. We will address our objectives with a two-step approach. First, we will examine the effects of pneumonia on the immune response within the myocardium and the gene expression profiles of cardiac cells using molecular and cell biology techniques, such as snRNA sequencing, histology, mass cytometry, multi-omics analyses (including proteomics and metabolomics), and in vitro studies on myocardial cells. Second, we will investigate the impact of pneumonia on cardiac remodeling and the development of heart failure under hypertensive conditions. Our goal is to understand the cellular and molecular mechanisms involved in pneumonia-induced (subclinical) cardiac remodeling and how these pathways contribute to heart failure development. Specifically, we aim to explore how pneumonia-related responses increase the susceptibility of the myocardium to heart failure, particularly under conditions of increased cardiovascular risk, such as in models of arterial hypertension. Our long-term goal is to establish targeted preventive strategies to reduce the risk of heart failure following CAP in high-risk patients with comorbidities, including hypertension.

• DFG Programme: Research Grants