Converging mechanisms for thoracic aortic aneurysm and dissection: dissecting the transcriptomic landscape of the diseased aorta.

Progressive dilatation of the aorta leads to the development of thoracic aortic aneurysms (TAAs), frequently resulting in aortic dissection or rupture. The latter events associate with an ultimate mortality rate of 50% and, hence, represent a prominent cause of morbidity and mortality in the Western population. Prophylactic surgery of TAA patients reduces the mortality rate down to about 5%, but comes with a relatively high risk of complications. Medical therapies capable of stopping or even reversing aneurysm formation are clearly highly needed, but are not available yet. Further deciphering of the mechanisms underlying TAA is essential to develop more efficient drugs. Owing to the advent of -omics technologies, it is now possible to dig into pan-TAA pathomechanisms in a hypothesis-free manner, opening new avenues to discover yet unexplored disease pathways and, hence, novel therapeutic targets. With this project, we want to be the first to take up the challenge of discovering convergent disease-linked pathways for TAA in a hypothesis-free manner using mouse and iPSC-derived cell models. The anticipated findings will advance the pathomechanistic TAA knowledge significantly beyond the current understanding and will greatly facilitate the development of novel therapeutic strategies.

Keywords:HEREDITARY, MOUSE MODELS, THORACIC AORTIC ANEURYSM, CARDIOGENETICS

Disciplines:Vascular diseases, Cell signalling, Cellular interactions and extracellular matrix, Genetics