Abstract Th0008: The Role of Perivascular Adipose Tissue-Derived Disintegrin and Metalloproteinase 12 in Abdominal Aortic Aneurysm Formation

Abdominal aortic aneurysm (AAA) is a leading cause of death worldwide. Due to the limited understanding of the pathogenesis of AAA, the therapeutic options are lack of drug-based treatment but limited to surgical repair to prevent vessel rupture. Perivascular adipose tissue (PVAT) surrounds the aorta and shares common features with brown adipose tissue (BAT). As an integral and functional layer of aorta, PVAT involves in the regulation of vascular homeostasis through paracrine system. Recently, there is accumulating evidence suggested that dysfunctional PVAT promotes AAA progression. Extracellular matrix (ECM) remodeling is a significant characteristic of AAA. As ECM proteases, a disintegrin and metalloproteases (ADAMs) involved in the regulation of cardiovascular function. Previous studies reveal that peri-microvascular ADAM12 contributes to tissue fibrosis and damage. However, whether PVAT ADAM12 involves in macrovascular physio-pathological process is unclear. It is well regarded that the same factor may have disparate functions in different tissues. Therefore, the purpose of this study is to explore whether and how PVAT ADAM12 affect AAA progression. Using high-fat diet (HFD) and hypertensive mouse model, we demonstrated that ADAM12 expression will increase in PVAT under pathological condition. Mice with brown-adipocyte specific ADAM12 knockout showed more severe Ang II (Angiotensin II)-induced AAA. These data indicated that PVAT ADAM12 is critical for maintaining vascular homeostasis and deficiency of ADAM12 contributes to AAA progression.