Trigger mechanisms and micro-RNA-related regulation of inflammasomes in abdominal aortic aneurysm

• Applicant: Dr. Markus Wagenhäuser
• Subject Area: General and Visceral Surgery
• Term: from 2015 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 290076834

Project Description Abdominal aortic aneurysm (AAA) is a lethal disease if rupture occurs in the late stages. Non-invasive therapeutic strategies that significantly limit AAA growth or prevent development do not yet exist, in part because the responsible underlying molecular mechanisms are not completely understood. AAA disease is increasingly considered a sterile inflammatory disease. Triggering pathways and other regulatory elements such as post-transcriptional micro-RNA (miR) dependent gene expression modulation might be targets for therapeutic strategies. Inflammasomes such as Nod-like receptor family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) are components of the innate immune system. When activated they form oligomeric protein complexes, causing maturation of cytokine precursors like IL-1B and IL-18. Today, there is limited knowledge regarding the trigger mechanisms and post-transcriptional gene regulation of inflammasomes in AAA disease. High cytosolic levels of reactive oxygen species (ROS), Cathepsin B (Cat B) and dsDNA have been proposed as possible triggers. Their role in the inflammasome activation cascade will be investigated using two independent murine models of aneurysm induction being employed in the host laboratory. Using these murine models, the regulatory impact of miR-223, miR-30, miR-143 and the miR-23a/b family on inflammasome activation will be analysed.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Philip S. Tsao, Ph.D.