VNS improves VSMC metabolism and arteriogenesis in infarcted hearts through m/n-AChR-Akt-SDF-1α in adult male rats

IF 2.9 4区 生物学 Q3 CELL BIOLOGY
Xing-yuan Li, Jia-Qi Liu, Yan Wang, Yan Chen, Wen-hui Hu, Yan-xia Lv, Yan Wu, Jing Lv, Jun-ming Tang, Deying Kong
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引用次数: 0

Abstract

Vagal nerve stimulation (VNS) provides a novel therapeutic strategy for injured hearts by activating cholinergic anti-inflammatory pathways. However, little information is available on the metabolic pattern and arteriogenesis of VSMCs after MI. VNS has been shown to stimulate the expression of CPT1α, CPT1β, Glut1, Glut4 and SDF-1α in coronary VSMCs, decreasing the number of CD68-positive macrophages while increasing CD206-positive macrophages in the infarcted hearts, leading to a decrease in TNF-α and IL-1β accompanied by a reduced ratio of CD68- and CD206-positive cells, which were dramatically abolished by atropine and mecamylamine in vivo. Knockdown of SDF-1α substantially abrogated the effect of VNS on macrophagecell alteration and inflammatory factors in infarcted hearts. Mechanistically, ACh induced SDF-1α expression in VSMCs in a dose-dependent manner. Conversely, atropine, mecamylamine, and a PI3K/Akt inhibitor completely eliminated the effect of ACh on SDF-1α expression. Functionally, VNS promoted arteriogenesis and improved left ventricular performance, which could be abolished by Ad-shSDF-1α. Thus, VNS altered the VSMC metabolism pattern and arteriogenesis to repair the infarcted heart by inducing SDF-1α expression, which was associated with the m/nAChR-Akt signaling pathway.

VNS 通过 m/n-AChR-Akt-SDF-1α 改善成年雄性大鼠梗死心脏中 VSMC 的新陈代谢和动脉生成
摘要 迷走神经刺激(VNS)通过激活胆碱能抗炎通路,为损伤心脏提供了一种新的治疗策略。然而,有关心肌梗死后 VSMC 的代谢模式和动脉生成的信息却很少。研究表明,VNS 能刺激冠状动脉 VSMCs 中 CPT1α、CPT1β、Glut1、Glut4 和 SDF-1α 的表达,减少 CD68 阳性巨噬细胞的数量,同时增加梗死心脏中 CD206 阳性巨噬细胞的数量,导致 TNF-α 和 IL-1β 的减少,CD68 阳性和 CD206 阳性细胞的比例也随之降低,阿托品和甲氰咪胍在体内能显著消除这些效应。SDF-1α的敲除大大减弱了VNS对梗死心脏巨噬细胞改变和炎症因子的影响。从机理上讲,乙酰胆碱以剂量依赖的方式诱导血管内皮细胞中 SDF-1α 的表达。相反,阿托品、麦角胺和 PI3K/Akt 抑制剂完全消除了 ACh 对 SDF-1α 表达的影响。在功能上,VNS促进了动脉生成并改善了左心室功能,而Ad-shSDF-1α可消除这种作用。因此,VNS通过诱导SDF-1α的表达改变了VSMC的代谢模式和动脉生成,从而修复了梗死的心脏,这与m/nAChR-Akt信号通路有关。
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来源期刊
Journal of Molecular Histology
Journal of Molecular Histology 生物-细胞生物学
CiteScore
5.90
自引率
0.00%
发文量
68
审稿时长
1 months
期刊介绍: The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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