Congenital heart diseases and right heart failure: The impact of the regulatory miRNA-mRNA network on progression and pathophysiology

• Applicant: Dr. Franziska Pankratz
• Subject Area: Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 559333870

Over the past decades, major advances have been made in the diagnosis and treatment of congenital heart diseases and many children are surviving into adulthood, making a life-long specialized care necessary. Congenital heart diseases encompass a wide spectrum of pathologies, and right ventricular failure is a very frequent complication in this population, resulting in specific therapeutic challenges that differ from the treatment of left ventricular disease. Here, I aim to investigate regulatory RNA-networks in right ventricular dysfunction using miRNA sequencing and additional whole transcriptome analysis. I will apply two different established mouse models of right ventricular stress to induce either volume (aortocaval shunt) or pressure (pulmonary artery constriction, PAC) overload of the right ventricle. Following the identification of candidates of interest, their characterization in the models of right ventricular stress, and comparisons with an expression analysis in human patient samples, I will focus on their direct and indirect target genes and the corresponding signaling networks. Besides sequencing-based global transcriptome analysis of the right ventricle, I will include single cell sequencing following RNA-modulation to identify cell-specific regulatory networks in right ventricular dysfunction. Finally, I will investigate the possibility of a RNA-based therapy to improve right ventricular function using state of the art techniques for in vivo modulation of regulatory RNA expression level. With this project, I aim for a better understanding of the biomechanics and the structural, mechano-electrical and molecular remodeling processes during right ventricular stress, fibrosis and failure, a highly under-investigated area of cardiovascular disease.

• DFG Programme: Research Grants