Role of long non-coding RNA CRNDE in the pathophysiology of thoracic aortic aneurysm - an in vitro analysis.

• Applicant: Dr. Joscha Büch
• Subject Area: Cardiac and Vascular Surgery
• Term: from 2021 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 499142384

Thoracic aortic aneurysm (TAA) is an underestimated disease with a substantial risk of dissection and rupture. Pathophysiologically, degeneration of the tunica media occurs. In this process, vascular smooth muscle cell dynamics and apoptosis play a crucial role. Preliminary results from single-cell RNA sequencing, identified exclusive expression of CRNDE in vascular smooth muscle cells. CRNDE is a long non-coding RNA (lncRNA) that inhibits apoptosis and promotes proliferation and migration. Preliminary quantitative PCR results from TAA tissue revealed decreased expression of CRNDE in dilated areas compared with intraindividual controls of less dilated areas. Based on these results, this lncRNA may be thought to play a key role in the regulation of smooth muscle cell dynamics and apoptosis in thoracic aortic aneurysm.The overall goal of the proposed research project is to evaluate the role of the lncRNA CRNDE in the context of thoracic aortic aneurysm in vitro.Small interfering RNA (siRNA)-induced inhibition and lentiviral overexpression of CRNDE in primary vascular smooth muscle cells from TAA tissue will provide a better understanding of the regulatory potential of this lncRNA and thus a deeper insight into the pathophysiology of thoracic aortic aneurysm. Quantitative PCR analysis of TAA tissue will be used to investigate any difference in CRNDE expression with respect to cofactors such as aortic valve morphology and function or comorbidities. Fluorescence microscopy will be used to visualize the exact localization of CRNDE expression in TAA tissue sections. Furthermore, using the new aorta-on-a-chip assay, the potential for therapeutic and diagnostic approaches of CRNDE in the context of TAA will be elucidated. The results from this project may provide a deeper understanding of the pathophysiology of thoracic aortic aneurysm and, in this context, shed light on the role of CRNDE, a promising long non-coding RNA.

• DFG Programme: Research Grants