Role of NFAT in the Progression of Diabetic Atherosclerosis.

Role of NFAT in the Progression of Diabetic Atherosclerosis.
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DOI:
10.3389/fcvm.2021.635172
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发表时间:
2021
影响因子:
3.6
通讯作者:
Li L
Li L
中科院分区:
医学3区
文献类型:
--
作者:
Cai Y;Yao H;Sun Z;Wang Y;Zhao Y;Wang Z;Li L

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活化T细胞核因子(NFAT)是一种具有多向调节功能的转录因子,广泛表达于免疫细胞,包括心血管系统细胞和非免疫细胞。大量研究证实钙调神经磷酸酶/NFAT信号转导在胚胎发育过程中血管系统和心血管系统的发育中非常重要,在动脉粥样硬化、血管钙化、高血压等血管疾病的发生中发挥一定作用。最近的体外和体内研究表明,NFAT蛋白及其在细胞核中的激活和与DNA相关位点的结合可以很容易地诱导下游靶基因的表达,这些靶基因参与各种病理生理状态下血管壁相关细胞的增殖、迁移、血管生成和血管炎症。 NFAT 表达受多种信号通路调节,包括 CD137-CD137L 和 OX40-OX40L 通路。作为一种功能多样的转录因子,NFAT 与大量信号分子相互作用,调节细胞内和细胞外信号通路。这些以NFAT为中心的信号通路在动脉粥样硬化的进展中发挥着重要的调节作用,例如在血管平滑肌细胞表型转变和迁移、内皮细胞损伤、巨噬细胞衍生的泡沫细胞形成和斑块钙化中。 NFAT及相关信号通路为动脉粥样硬化等血管疾病提供了新的治疗靶点。因此,进一步研究NFAT在动脉粥样硬化发生和演变中的作用机制仍然至关重要。
Nuclear factor of activated T cells (NFAT) is a transcription factor with a multidirectional regulatory function, that is widely expressed in immune cells, including cells in the cardiovascular system, and non-immune cells. A large number of studies have confirmed that calcineurin/NFAT signal transduction is very important in the development of vascular system and cardiovascular system during embryonic development, and plays some role in the occurrence of vascular diseases such as atherosclerosis, vascular calcification, and hypertension. Recent in vitro and in vivo studies have shown that NFAT proteins and their activation in the nucleus and binding to DNA-related sites can easily ɨnduce the expression of downstream target genes that participate in the proliferation, migration, angiogenesis, and vascular inflammation of vascular wall related cells in various pathophysiological states. NFAT expression is regulated by various signaling pathways, including CD137-CD137L, and OX40-OX40L pathways. As a functionally diverse transcription factor, NFAT interacts with a large number of signaling molecules to modulate intracellular and extracellular signaling pathways. These NFAT-centered signaling pathways play important regulatory roles in the progression of atherosclerosis, such as in vascular smooth muscle cell phenotypic transition and migration, endothelial cell injury, macrophage-derived foam cell formation, and plaque calcification. NFAT and related signaling pathways provide new therapeutic targets for vascular diseases such as atherosclerosis. Hence, further studies of the mechanism of NFAT in the occurrence and evolution of atherosclerosis remain crucial.
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