Lack of evidence for the involvement of non-canonical pyroptosis in a mouse model of thoracic aortic dissection.

Thoracic aortic dissection (TAD) is a severe aortic disease with high mortality. One of its pathological hallmarks is aortic smooth muscle cell death, but the death modalities are not fully known. Recent studies suggest an association of pyroptosis with aortic diseases, but whether it contributes to TAD remains unknown. Here, we modeled TAD by feeding 3-week-old mice with β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, for 28 days. By means of global knockout of Caspase11 and Gsdmd in mice, two key knots in non-canonical pyroptosis pathway, we showed that neither Caspase11-/- nor Gsdmd-/- influenced TAD phenotypes, including death rate, aortic lesions. This pilot study on pyroptosis yields no positive outcome, but is informative and thought-provoking. It highlights factors to consider when designing future experiments, including conditional gene knockout, multiple model validation, and extensive Caspases screening. The role of pyroptosis in TAD warrants further investigations through more precise methodologies in more animal models.