Koyama Teruhide, Sakurai Takayuki, Kamiyoshi Akiko, Ichikawa-Shindo Yuka, Kawate Hisaka, Shindo Takayuki
Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science. 2) Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan.
J Atheroscler Thromb. 2015 Jul 23;22(7):647-53. doi: 10.5551/jat.29967. Epub 2015 Jun 4.
Vascular endothelial cells play key roles in maintaining vascular and organ homeostasis. Adrenomedullin (AM), originally identified as a vasodilating peptide, is now recognized to be a pleiotropic molecule involved in both circulatory homeostasis and the pathogenesis of cardiovascular diseases. We have reported that knockout mice deficient in AM or receptor activity-modifying protein 2 (RAMP2), an AM-receptor accessory protein, show vascular endothelial cell deformities that are embryonically lethal. To directly clarify the pathophysiological functions of the vascular AM-RAMP2 system, we generated vascular endothelial cell-specific RAMP2 knockout mice. Using these mice, we found that the AM-RAMP2 system is a key determinant of vascular integrity and homeostasis from prenatal stages through adulthood. This review highlights the functions of AM-RAMP2 in vascular endothelial cells.
血管内皮细胞在维持血管和器官稳态中发挥关键作用。肾上腺髓质素（AM）最初被鉴定为一种血管舒张肽，现在被认为是一种多效性分子，参与循环稳态和心血管疾病的发病机制。我们已经报道，缺乏AM或受体活性修饰蛋白2（RAMP2，一种AM受体辅助蛋白）的基因敲除小鼠表现出胚胎致死的血管内皮细胞畸形。为了直接阐明血管AM-RAMP2系统的病理生理功能，我们构建了血管内皮细胞特异性RAMP2基因敲除小鼠。利用这些小鼠，我们发现AM-RAMP2系统是从产前阶段到成年期血管完整性和稳态的关键决定因素。这篇综述重点介绍了AM-RAMP2在血管内皮细胞中的功能。
