Cardiovascular disease and mTOR signaling.
Cardiovascular disease and mTOR signaling.
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DOI：
10.1016/j.tcm.2012.04.005
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发表时间：
2011-07
影响因子：
9.3
通讯作者：
Maiese K
中科院分区：
文献类型：
--
作者：
Chong ZZ;Shang YC;Maiese K
哺乳动物雷帕霉素靶蛋白（mTOR）的细胞信号传导途径本质上是广泛的，但通过mTORC 1和mTORC 2的蛋白质复合物紧密整合。虽然这两种复合物共享一些相似的子组分，mTORC 1主要与调节蛋白Raptor相关，而mTORC 2依赖于Rictor。与Wnt以及生长因子信号传导合作的mTOR途径对于内皮细胞和心肌细胞生长至关重要。在成熟分化的内皮细胞和心肌细胞中，mTOR活化在氧化应激期间调节凋亡和自噬途径，其可依赖于蛋白激酶B（Akt）的活化。mTOR的这些保护途径可以促进血管生成并限制急性细胞死亡，以促进心脏修复和组织再生。然而，在某些情况下，阻断mTOR通路可能是限制血管病变和促进微循环流动所必需的。进一步阐明mTOR的重要调控途径的未来工作可以为心血管疾病的治疗提供新的治疗见解。
The cell signaling pathways of the mammalian target of rapamycin (mTOR) are broad in nature, but are tightly integrated through the protein complexes of mTORC1 and mTORC2. Although both complexes share some similar subcomponents, mTORC1 is primarily associated with the regulatory protein Raptor while mTORC2 relies upon Rictor. Pathways of mTOR that partner with Wnt as well as growth factor signaling are vital for endothelial and cardiomyocyte growth. In mature differentiated endothelial cells and cardiac cells, mTOR activation regulates both apoptotic and autophagic pathways during oxidative stress that can be dependent upon the activation of protein kinase B (Akt). These protective pathways of mTOR can promote angiogenesis and limit acute cell death to foster cardiac repair and tissue regeneration. However, under some conditions, blockade of mTOR pathways may be necessary to limit vasculopathy and promote microcirculatory flow. Future work that further elucidates the vital regulatory pathways of mTOR can offer new therapeutic insights for the treatment of cardiovascular diseases.