Necroptosis in aortic aneurysm disease - significance of inflammation in MLKL dependent cell death (B05)

• Subject Area: Cardiology, Angiology ; Immunology ; Parasitology and Biology of Tropical Infectious Disease Pathogens ; Virology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 397484323

Regulated cell death of aortic smooth muscle cells represents a hallmark of aortic aneurysm formation. In the first funding period, we have shown that the mixed lineage kinase-like pseudokinase (MLKL)-dependent inhibition of necroptosis, a specific form of regulated cell death, mitigates abdominal aortic aneurysm disease in mice. To underline the translational potential of these findings, we now aim to establish a large animal model of pharmaceutical MLKL inhibition in pigs. Additionally, we will characterise the impact of MLKL-dependent necroptosis-inhibition on models of thoracic aortic aneurysm disease, a condition connected with Marfan’s syndrome and driven by dysregulation of cell death and matrix formation and thereby a very promising target for MLKL-alteration.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 259: Aortic Disease
• Applicant Institution: Rheinische Friedrich-Wilhelms-Universität Bonn
• Project Heads: Privatdozent Dr. Matti Adam; Professorin Dr. Ana Jesús Garcia Sáez, since 7/2023; Professor Dr. Manolis Pasparakis, until 6/2023