β-aminopropionitrile-induced thoracic aortopathy is refractory to cilostazol and sildenafil in mice

Thoracic aortopathies are life-threatening diseases including aneurysm, dissection, and rupture. Phosphodiesterases (PDEs) regulate intracellular cyclic nucleotide concentrations. Recent studies report the influences of cilostazol, a PDE3 inhibitor, and sildenafil, a PDE5 inhibitor, on abdominal aortic aneurysm formation. However, their impacts on thoracic aortopathy remain unknown. In this study, we investigated whether cilostazol and sildenafil affect thoracic aortopathy induced by β-aminopropionitrile (BAPN) administration in mice. Bulk RNA sequencing analysis revealed that BAPN administration upregulated <i>Pde3a</i> transcription in the ascending aorta and <i>Pde5a</i> in both ascending and descending regions before thoracic aortopathy formation. Next, we tested the effects of cilostazol or sildenafil on BAPN-induced thoracic aortopathy. BAPN-administered mice were fed a diet supplemented with either cilostazol or sildenafil. Mass spectrometry measurements determined the presence of cilostazol or sildenafil in the plasma of mice fed drug-supplemented diets. However, neither drug altered BAPN-induced aortic rupture nor aneurysm formation and progression. These results provide evidence that cilostazol and sildenafil did not influence BAPN-induced thoracic aortopathy in mice.