Abstract: Absent in Melanoma 2(AIM2), a member of the PYHIN(Containing Pyrin and HIN domain proteins) families, plays an important role in sensing dsDNA and assembling AIM2 inflammatory bodies. AIM2 inflammasome, with pro-inflammatory and pro-pyrolytic properties, is closely related to the occurrence and development of cardiovascular diseases. It can be activated in atherosclerotic plaques, aortic aneurysm walls and damaged myocardium, and its activation is strictly regulated by a variety of factors. We summarize the latest knowledge of AIM2 biology and provide new insights into the mechanisms and roles of different factors in AIM2 inflammasome activation. In addition, we explore the interaction between AIM2 and the pathology of atherosclerosis, aortic aneurysm, myocardial infarction, and heart failure. A better understanding of the pathological role of AIM2 in cardiovascular disease will facilitate the development of new therapies.