Production and Signaling Mechanism of Adorenomedullin in Cardiovascular Cells

肾上腺髓质素（AM）是从人嗜铬细胞瘤组织中分离出来的一种有效的血管松弛肽。AM的mRNA在心脏和血管壁细胞中高表达，AM可能在心血管疾病中起重要作用。在本项目中，我们研究了AM的基因表达和分泌，并探讨了AM在心力衰竭和肺动脉高压中的病理生理意义。1)在内毒素休克或心肌梗死模型动物中，AM基因在心血管组织中有明显的表达诱导作用，AM可能是这些疾病的抗损伤因素之一。2)缺氧条件下心肌细胞AM分泌增加可能与氧化应激有关。肌细胞分泌的AM可能以自分泌的方式发挥细胞保护作用。3)缺血再灌注AM可减轻大鼠左室重构和心肌纤维化的发生。AM的心脏保护作用可能至少部分归因于其抗凋亡作用。4)在人体研究中，静脉输注AM对充血性心力衰竭或毛细血管前肺动脉高压患者具有有益的血流动力学和激素作用。AM及其药物配体应该在心血管疾病的治疗中被证明是有用的。

Adrenomedullin (AM) is a potent vasorelaxant peptide isolated from human pheochromocytoma tissue. mRNA of AM is highly expressed in the cells of heart and vascular wall, and AM may play an important role in cardiovascular diseases.In this project, we have studied the gene expression and secretion of AM, and also examined the pathophysiological significance of AM in heart failure and pulmonary hypertension.1) In the model animals of endotoxin shock or myocardial infarction, marked induction of AM gene expression was observed in the cardiovascular tissues, and AM may be one of the factors acting against damage in these diseases.2) An oxidative stress may be involved in the increased AM secretion from cardiac myocytes under hypoxic condition. AM secreted from myocytes may play a cell protective role in an autocrine manner.3) AM infusion during ischemia/reperfusion attenuated the development of LV remodeling and myocardial fibrosis in rats. The cardioprotective effects of AM may be attributed at least partly to its anti-apoptotic effect.4) In human studies, intravenous infusion of AM has beneficial haemodynamic and hormonal effects in patients with congestive heart failure or precapillary pulmonary hypertension. AM and its pharmaceutical ligands should prove useful in the treatment of cardiovascular diseases.