Extracellular vesicles and regulatory RNAs as intercellular messengers in aortic disease (B04)

• Subject Area: Cardiology, Angiology ; Anatomy and Physiology ; Cell Biology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 397484323

This project aims to decipher RNA-mediated mechanisms of intercellular communication via extracellular vesicles (EVs)/ncRNAs in the aortic valve (AV) and heart in aortic valve stenosis (AS). Our recent work shows that miRNAs can control gene expression of disease-relevant genes and cellular function during AS. Other heterogeneous subclasses of ncRNAs, namely circRNAs, and lncRNAs, have also been shown to control gene expression (epigenetically) and regulate cellular functions in many CVDs. The transcriptome signature of patient-derived EVs, AV cells, and AV tissues, using NGS and PCR-based arrays, revealed numerous dysregulated genes (mRNAs), miRNAs, lncRNAs, and circRNAs in comparison to controls. By using primary valvular cells from patient AV explants and the murine AS model, we aim to gain more mechanistic insight into the mode of action of ncRNAs and develop potential RNA-based therapeutics. Furthermore, we will study the effects of extrinsic factors (e.g., shear stress and mechanical strain) since changes in flow dynamics, mechanical forces, and epigenetic regulators can be conveyed via the noncoding transcriptome and appear to be central to the development and progression of AS.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 259: Aortic Disease
• Applicant Institution: Rheinische Friedrich-Wilhelms-Universität Bonn
• Project Heads: Dr. Philip Roger Goody, since 7/2023; Dr. Mohammed Rabiul Hosen, Ph.D., since 7/2023; Privatdozent Dr. Felix Jansen, until 9/2023; Professor Dr. Alexander Pfeifer, until 6/2023