Aortic dissection is highly lethal, and the risk factors such as hypertension, aging, and atherosclerosis are thought to contribute to its onset. Recently, there has been increasing reports that vascular endothelial growth factor (VEGF) inhibitors can induce the aortic dissection as an adverse event. However, the association between VEGF inhibitors and aortic dissection has been unclear. Therefore, we investigated if VEGF inhibitor increases the onset of aortic dissection using acute aortic dissection model mice (AAD mice).
Sunitinib (100 mg/kg/day) was administered orally for 28days to AAD mice induced by nitric oxide inhibitor, angiotensin II, and lysyl oxidase inhibitor. Blood pressure was measured every week. After 28days, the incidence rate of AAD was estimated. For in vitro study, human umbilical vein endothelial cells (HUVEC) were treated by sunitinib for 24 hours. Then, mRNA expressions of intracellular cell adhesion molecule-1 (ICAM-1) and endothelin-1 (ET-1) were measured.  
Sunitinib increased systolic blood pressure (182 mmHg vs 288 mmHg with sunitinib ; p＜0.01) and the incidence of AAD (40% vs 59% with sunitinib; p=0.26). Moreover, sunitinib increased mRNA expressions of ICAM-1 and ET-1 in HUVEC. These results suggested that VEGF inhibitors induced high blood pressure and developed AAD via endothelial damage.