Development of new therapies and significance of adrenomedullin and mast cells in the abdominal aortic aneurysm.

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Abdominal aortic aneurysm (AAA) develops based on advanced atherosclerosis; however, the underlying pathogenesis remains unknown. Adrenomedullin (AM) is widely expressed in various organs and tissues, and has anti-inflammatory, anti-oxidant and angiogenic activity. We have reported that AM is produced in mast cells of human AAA and that AM exhibited the anti-fibrotic activity on fibroblasts. We investigated the role of AM in the development of AAA in 12 weeks-old male apoE-/- mice bred with AM heterozygous, or its role when recombinant human (rh)AM was administrated to the apoE-/- male mice, which was infused with 1000ng/kg/min of angiotensin II for 28 days. Mortality tended to be higher in rhAM at 3000ng/kg/hr. Both the incidence and the size of AAA were not significant between the groups. Because of dual nature of AM action on progression or protection of AAA, we may not have observed the biological actions of AM in the development of AAA.