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糖尿病引起的金属离子水平的改变会降低MMPs的活性,从而降低大动脉动脉瘤风险

Han Nie¹, Zi-Sheng Huang², Geng Liu¹

¹Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan; Department of Stem Cell Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

|November 16, 2024

概括

糖尿病通过改变金属离子水平来降低大动脉动脉瘤风险,从而降低矩阵金属蛋白酶 (MMP) 活性. 在糖尿病小鼠中补充可以使这些变化正常化,这表明大动脉动脉瘤的治疗策略.

科学领域:

生物化学生化学
心血管生物学心血管生物学
代谢疾病代谢疾病

背景情况:

糖尿病 (DM) 与心血管疾病风险有关.
矛盾的是,糖尿病患者群体表现出大动脉动脉瘤发育的减少.
矩阵金属蛋白酶 (MMPs) 参与大动脉动脉瘤的发病.

研究的目的:

调查DM诱导的金属离子水平变化是否会降低MMP活性,从而降低大动脉动脉瘤风险.
探索糖尿病,金属离子,MMP和大动脉动脉瘤之间的机制联系.

主要方法:

在高葡萄糖条件下培养血管光滑肌细胞 (VSMC) 和巨细胞.
建立了一种小鼠模型,用于与腹腔大动脉动脉瘤相关的链毒素诱导的糖尿病.
给糖尿病小鼠服用补充剂.
分析了血清金属离子水平 (Zn2+,Mg2+),动脉瘤大小,基因表达 (纤维素,CTGF) 和MMP活性 (MMP2,MMP9).
相关的临床数据DM,血清Zn2+水平和大动脉动脉瘤风险.

主要成果:

高葡萄糖增加了VSMC中的纤维素和CTGF,并在巨细胞中增加了MMP2/MMP9.
糖尿病小鼠表现出较低的血清Zn2+和Mg2+,较小的动脉瘤,以及更高的纤维素/CTGF表达.
补充剂在糖尿病小鼠中逆转了这些效应.
MMP2的酶活性是由Zn2+和Mg2+度调节的.
临床数据证实了DM,血清Zn2+水平和大动脉动脉瘤风险之间的相关性.

结论:

金属离子水平的DM诱导的变化,特别是,降低MMP活性.
这种MMP活动的减少似乎会在糖尿病患者中否定大动脉动脉瘤的发展.
这些发现提供了新的机制性见解和对大动脉动脉瘤的潜在治疗策略.

关键词:

大动脉动脉瘤是一个大动脉动脉瘤.糖尿病是一种糖尿病.在MMPs活动中,MMPs是指MMPs的活动.金属离子水平水平.

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