谷氨酰胺通过调节血管内皮细胞凋亡和 M1 型巨噬细胞活化保护小鼠腹主动脉瘤

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-05-19 eCollection Date: 2024-01-01 DOI:10.7150/ijms.96395
Jinxi Wang, Xingwen Da, Yifei Chen, Ancai Yuan, Jun Pu
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引用次数: 0

摘要

谷氨酰胺(Gln)被称为最丰富的游离氨基酸,广泛存在于人体内。在这项研究中,我们证实了谷氨酰胺对血管紧张素Ⅱ(AngⅡ)和磷酸钙(Ca3(PO4)2)在体内诱发的小鼠腹主动脉瘤(AAA)的保护作用,其特点是降低了小鼠AAA的发病率。此外,组织形态学染色直观地显示,谷氨酰胺处理的小鼠腹主动脉弹性纤维更完整,胶原沉积更少。此外,我们还发现谷氨酰胺抑制了小鼠肾上性腹主动脉中活性氧化物(ROS)的过度产生、基质金属蛋白酶(MMP)的活性、M1巨噬细胞的活化以及血管平滑肌细胞(VSMC)的凋亡、此外,谷氨酰胺还能下调经 AngII 处理的细胞中高表达的 MMP-2 蛋白、MMP-9 蛋白、促凋亡蛋白、IL-6 蛋白和 TNF-α 蛋白及 mRNA 水平。总之,这些结果表明谷氨酰胺通过抑制血管内皮细胞凋亡、M1巨噬细胞活化、氧化应激和细胞外基质降解来保护小鼠AAA。
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Glutamine Protects against Mouse Abdominal Aortic Aneurysm through Modulating VSMC Apoptosis and M1 Macrophage Activation.

Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca3(PO4)2) in vivo, which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what's more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.

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