The contributions included the following: (a) Hint1 deficiency in VSMCs alleviates aortic aneurysm formation and progression; (b) the driving role of HINT1 in aortic aneurysm is dependent on ITGA6; (c) ITGA6 promotes aortic aneurysm by activating the downstream FAK/STAT3 signal pathway; and (d) HINT1 upregulates ITGA6 transcription by interacting with and activating TFAP2A, which is the transcription factor of ITGA6. Here, STAT3 is linked to aortic aneurysm.