Adrenomedullin Does Not Contribute toward the Development of Abdominal Aortic Aneurysm in Mice

Abstract

Abdominal aortic aneurysm (AAA) develops based on advanced atherosclerosis; however, the underlying pathogenesis remains unknown. Adrenomedullin (AM) is widely expressed in various human and rodent tissues, and has been reported to protect blood vessels. We have previously reported that AM is produced in mast cells of human AAA and that AM exhibited the antifibrotic activity of mast cell-derived AM on fibroblasts. In the present study, we investigated the role of AM in the development of AAA in 12-week-old male apolipoprotein (apo)E ﹣/﹣ mice bred with AM heterozygous, or its role when recombinant human (rh) AM was administrated to the apoE ﹣/﹣ male mice, which was infused with 1000 ng/kg/min of angiotensin II (Ang II) for 28 days. The incidence of the development of AAA in Ang II-infused apoE ﹣/﹣ AM ﹢/﹣ mice did not change compared with that in apoE ﹣/﹣ mice (33.3% vs. 47.4%, p = 0.2333). In addition, rhAM administration had little effect on the incidence of the development of AAA formation (AM: 0 ng/kg/hr 47.4%; 300 ng/kg/hr 36.4%; 3000 ng/kg/hr 27.3%; p = 0.2595). In conclusion, this study suggests that AM does not contribute toward the development of AAA.