W. Ageedi1, P. Ren1, Y. Wang1, J. Guo1, J. Coselli1,2,3, Y. Shen1,2,3, S. LeMaire1,2,3 1Baylor College Of Medicine,Division Of Cardiothoracic Surgery, Michael E. DeBakey Department Of Surgery,Houston, TX, USA 2Texas Heart Institute,Cardiovascular Surgery,Houston, TX, USA 3Baylor College Of Medicine,Department Of Molecular Physiology And Biophysics,Houston, TX, USA
Introduction: Ascending thoracic aortic aneurysms and dissections (AAD) are extremely lethal conditions. No effective medical treatment to prevent AAD currently exists. Identifying the biological pathways responsible for aortic destruction is critical for developing effective treatment. We have recently shown that NLRP3 (nucleotide oligomerization domain–like receptor family, pyrin domain containing 3)–caspase-1 inflammasome cascade degrades smooth muscle cell contractile proteins, leading to aortic biomechanical dysfunction and AAD development. Increasing evidence suggests that Absent In Melanoma 2 (AIM2), another member of the inflammasome family with cytosolic DNA sensing ability, is critically involved in tissue inflammation and destruction.We hypothesized that patients with ascending AAD have elevated aortic tissue levels of AIM2
Methods: Ascending aortic tissues were obtained from patients with ascending aortic dissection (n=6), patients with ascending aortic aneurysm without dissection (n=6) and organ-donor controls without aortic disease (n=6). We excluded patients with heritable aortic diseases, such as Marfan syndrome. AIM2 expression levels were determined by western blot and immunofluorescence analyses and compared between the three groups.
Results: Western blot analysis showed that while AIM2 was barely detectable in control and non-dissection aortic aneurysm tissues, AIM2 was markedly increased in aortic dissection samples. Double immunofluorescence analysis showed a significant amount of AIM2 in the aortic media and adventitia of aortic dissection tissue, particularly in smooth muscle cells.
Conclusions: The expression of AIM2 inflammasome is increased in sporadic ascending aortic dissection. Further studies are needed to confirm this finding in larger samples, and to determine the role of AIM2 in aortic inflammation, extracellular matrix destruction, smooth muscle cell dysfunction, and AAD development.