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

腹主动脉瘤（AAA）的发展是基于晚期动脉粥样硬化;然而，其潜在的发病机制仍不清楚。肾上腺髓质素（Adrenomedullin，AM）广泛表达于多种器官和组织，具有抗炎、抗氧化和血管生成活性。 我们曾报道人腹主动脉瘤肥大细胞产生AM，AM对成纤维细胞具有抗纤维化活性。我们研究了AM在12周龄的雄性apoE-/-小鼠AAA的发展中的作用，这些小鼠与AM杂合子一起饲养，或者当将重组人（rh）AM给予apoE-/-雄性小鼠时，其作用，该小鼠以1000 ng/kg/min的血管紧张素II输注28天。在3000 ng/kg/hr时，rhAM组的死亡率倾向于更高。AAA的发生率和大小在组间均不显著。由于AM对AAA的发展或保护作用的双重性质，我们可能没有观察到AM在AAA发展中的生物学作用。

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.