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Background  Phenotypic transformation of vascular smooth muscle cells is a key element in vascular remodeling and aortic aneurysm growth. Previously, deletion of several inflammasome components decreased formation of aortic aneurysm (AA) in the Angiotensin II (AngII) -induced mouse model. We hypothesized that the inflammasome sensor Absent in melanoma 2 (Aim2) might affect the phenotype of vascular smooth muscle cells (VSMC), thereby reducing AA formation.    Methods   Aim2−/−  mice and wild-type (WT) C57Bl/6 J mice were used as an animal model. VSMC were isolated from 6 months old mice and grown in vitro. Young (passage 3–5) and senescent (passage 7–12) cells were analyzed in vitro for calcification in mineralization medium by Alizarin Red S staining. Expression of calcification and inflammatory markers were studied by real-time RT-PCR and Western blotting, release of cytokines was determined by ELISA. To induce AA, osmotic mini-pumps loaded with AngII (1500 ng/kg bodyweight/min) were implanted for 28 days in male mice at 6 months of age.    Results  Compared with VSMC from WT mice, VSMC isolated from  Aim2−/−  mice were larger, less viable, and underwent stronger calcification in mineralization medium, along with induction of  Bmp4  and repression of  Tnfsf11/Rankl  gene expression. In addition,  Aim2  deficiency was associated with reduced inflammasome gene expression and release of Interleukin-6. Using the mouse model of AngII induced AA,  Aim2  deficiency reduced AA incidence to 48.4% (15/31) in  Aim2−/−  mice versus 76.5% (13/17) in WT mice. In contrast to  Aim2−/−  mice, AA from WT mice expressed significantly increased levels of alpha-smooth muscle actin/ Acta2 , indicating tissue remodeling. Reduced cell proliferation in  Aim2−/−  mice was indicated by significantly increased p16ink4a/ Cdkn2a  expression in untreated and AngII-infused aortas, and by significantly lower amounts of proliferating (Ki67 positive) VSMC in AngII-infused  Aim2−/−  mice.    Conclusions  Our results suggest a role for Aim2 in regulating VSMC proliferation and transition to an osteoblast-like or osteoclast-like phenotype, thereby modulating the response of VSMC in aortic remodeling and AA formation.

Deficiency in Aim2 affects viability and calcification of vascular smooth muscle cells from murine aortas and angiotensin-II induced aortic aneurysms