与ATIC相关的De Novo纯素合成在扩散性动脉疾病中具有关键作用

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Qian Ma^1,2, Qiuhua Yang², Jiean Xu²

¹State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, China (Q.M., Y.Z., M.H.).

|September 8, 2022

概括

在动脉疾病中,新生纯素合成促进了血管光滑肌细胞的增殖. 向ATIC酶可以抑制这一过程,从而为缩症等疾病提供潜在的治疗策略.

科学领域:

血管生物学
代谢途径
心血管疾病

背景情况:

血管光滑肌细胞 (VSMC) 的增殖是动脉疾病如静脉复缩的核心.
微粒细胞改变其新陈代谢,包括核酸合成,以支持增殖.
在动脉疾病中的VSMC增殖中,de novo精氨酸合成的具体作用仍未确定.

研究的目的:

研究新型 purin 合成在 VSMC 扩散中的作用.
确定ATIC酶在这个过程中的重要性.
评估ATIC作为动脉疾病的潜在治疗点.

主要方法:

使用液体染色体-并联质谱在增殖性VSMC中进行量化de novo纯素合成.
评估了新型VSMC中ATIC (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase) 的表达.
使用全球和VSMC特异性淘汰小鼠研究ATIC缺乏对新密和动脉样损伤形成的影响.

主要成果:

在增殖的VSMC中,de novo纯素合成升高.
在受损血管的内膜和动脉样硬化病变中,ATIC表达上调.
在疾病模型中,ATIC的淘汰显著抑制了增殖和减少了动脉新密度的形成.

结论:

在动脉疾病中,de novo纯素合成是支持VSMC增殖的关键途径.
在这个过程中,ATIC酶起着关键作用.
针对ATIC是一种有前途的治疗途径.

关键词:

美国动脉疾病动脉样硬化新生纯素合成扩散血管平滑肌细胞

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