Studies of pathophysiological role of Adrenomedullin-RAMP system using genetically modified RAMP mice

肾上腺髓质素（AM）是一种由多种组织分泌的血管活性肽，在抗炎、血管舒张和血管生成等方面起着重要作用。AM受体由两种蛋白组成；降钙素受体样受体（CRLR）和受体活性修饰蛋白（RAMP） 2或3。RAMPs的时空依赖性被认为对几种器官中独特的AM功能很重要。然而，RAMPs在AM-RAMPs系统中的作用和机制尚不清楚。在本研究中，我们利用血管内皮细胞特异性和心脏细胞特异性RAMP2KO小鼠研究RAMP2/3的病理生理作用，因为RAMP2KO在妊娠中期具有胚胎致死性，RAMP3KO包括RAMP2/RAMP3和RAMP3- tg小鼠。我们发现(1)基于AM的血管和器官保护作用，RAMP2对血管和心脏稳态至关重要(2)RAMP3参与炎症反应。

Adrenomedullin (AM) is a vasoactive peptide which is secreted by many tissues, and plays an important role in anti-inflammation, vasodilation and angiogenesis. AM receptor is composed of two proteins ; calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein (RAMP) 2 or 3. The space- and time-dependent use of RAMPs became suggested to be important for unique AM function in several organs. However, the mechanisms and roles of RAMPs in the AM-RAMPs system remain obscure. In this study, we investigated the pathophysiological role of RAMP2/3 using vascular endothelial cell-specific and cardiac cell-specific RAMP2 KO mice because of the embryonic lethal of RAMP2KO at mid-gestation, and RAMP3KO including RAMP2/RAMP3 and RAMP3-Tg mice. We have found that (1) RAMP2 is essential for vascular and cardiac homeostasis based on the vaso- and organ-protective effects of AM (2) RAMP3 is involved in inflammatory response.