Extracorporeal Cardiac Shock Waves Therapy Improves the Function of Endothelial Progenitor Cells After Hypoxia Injury via Activating PI3K/Akt/eNOS Signal Pathway.
Extracorporeal Cardiac Shock Waves Therapy Improves the Function of Endothelial Progenitor Cells After Hypoxia Injury via Activating PI3K/Akt/eNOS Signal Pathway.
复制标题
体外心脏冲击波疗法通过激活 PI3K/Akt/eNOS 信号通路改善缺氧损伤后内皮祖细胞的功能。
DOI：
10.3389/fcvm.2021.747497
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发表时间：
2021
影响因子：
3.6
通讯作者：
Cai H
中科院分区：
文献类型：
--
作者：
Wang M;Yang D;Hu Z;Shi Y;Ma Y;Cao X;Guo T;Cai H;Cai H
背景：体外心脏冲击波（ECSW）在冠心病的治疗中具有巨大的潜力。内皮祖细胞（Endothelial progenitor cells，EPCs）是一类来源于骨髓或外周血的多能祖细胞，具有向缺血心肌迁移并分化为成熟内皮细胞的能力，在血管新生和内皮修复中发挥重要作用。本研究旨在探讨ECSW治疗是否能改善缺氧诱导的EPCs功能障碍和凋亡，并探讨其可能机制。方法：从ApoE基因敲除大鼠骨髓中分离EPCs，采用流式细胞术和荧光染色法进行鉴定。采用内皮祖细胞建立体外缺氧损伤模型，分为6组：对照组、缺氧组、缺氧+ ECSW组、缺氧+LY 294002 + ECSW组、缺氧+ MK-2206 + ECSW组、缺氧+ L-NAME + ECSW组。将来自对照组、缺氧组和缺氧+ ECSW组的EPC用于mRNA测序反应。分别使用qRT-PCR和蛋白质印迹分析来分析mRNA和蛋白质表达水平。分别用CCK-8、流式细胞术、明胶、transwell和管形成来测量增殖、凋亡、粘附、迁移和血管生成。使用NO测定试剂盒测量一氧化氮（NO）水平。结果如下：京都基因和基因组百科全书（KEGG）富集分析显示差异表达基因在癌症信号传导、PI 3 K-Akt信号传导和Rap 1信号传导途径中富集。我们选择PI 3 K-Akt信号通路中的差异表达基因，并通过一系列实验进行验证。结果表明，ECSW（0.09mJ/mm ~ 2，500次）可显著提高缺氧损伤后EPCs的增殖、粘附、迁移和管腔形成能力，并上调p-PI 3 K、p-Akt、p-eNOS、Bcl-2蛋白和NO、PI 3 K和Akt mRNA的表达，下调Bax和Caspase 3蛋白的表达。ECSW的所有这些作用均使用PI 3 K（LY 294002）、Akt（MK-2206）和eNOS（L-NAME）特异性抑制剂消除。结论：ECSW主要通过激活PI 3 K/Akt/eNOS信号通路，抑制细胞凋亡，促进血管新生，对缺氧损伤的EPCs具有较强的修复作用，为ECSW治疗冠心病提供了新的证据。
Background: Extracorporeal cardiac shock waves (ECSW) have great potential in the treatment of coronary heart disease. Endothelial progenitor cells (EPCs) are a class of pluripotent progenitor cells derived from bone marrow or peripheral blood, which have the capacity to migrate to ischemic myocardium and differentiate into mature endothelial cells and play an important role in neovascularization and endothelial repair. In this study, we investigated whether ECSW therapy can improve EPCs dysfunction and apoptosis induced by hypoxia and explored the underlying mechanisms. Methods: EPCs were separated from ApoE gene knockout rat bone marrow and identified using flow cytometry and fluorescence staining. EPCs were used to produce in vitro hypoxia-injury models which were then divided into six groups: Control, Hypoxia, Hypoxia + ECSW, Hypoxia + LY294002 + ECSW, Hypoxia + MK-2206 + ECSW, and Hypoxia + L-NAME + ECSW. EPCs from the Control, Hypoxia, and Hypoxia + ECSW groups were used in mRNA sequencing reactions. mRNA and protein expression levels were analyzed using qRT-PCR and western blot analysis, respectively. Proliferation, apoptosis, adhesion, migration, and angiogenesis were measured using CCK-8, flow cytometry, gelatin, transwell, and tube formation, respectively. Nitric oxide (NO) levels were measured using an NO assay kit. Results: Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that differentially expressed genes were enriched in cancer signaling, PI3K-Akt signaling, and Rap1 signaling pathways. We selected differentially expressed genes in the PI3K-Akt signaling pathway and verified them using a series of experiments. The results showed that ECSW therapy (500 shots at 0.09 mJ/mm2) significantly improved proliferation, adhesion, migration, and tube formation abilities of EPCs following hypoxic injury, accompanied by upregulation of p-PI3K, p-Akt, p-eNOS, Bcl-2 protein and NO, PI3K, and Akt mRNA expression, and downregulation of Bax and Caspase3 protein expression. All these effects of ECSW were eliminated using inhibitors specific to PI3K (LY294002), Akt (MK-2206), and eNOS (L-NAME). Conclusion: ECSW exerted a strong repaired effect on EPCs suffering inhibited hypoxia injury by inhibiting cell apoptosis and promoting angiogenesis, mainly through activating the PI3K/Akt/eNOS signaling pathway, which provide new evidence for ECSW therapy in CHD.
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影响因子：
1.9
作者：
Burneikaitė G;Shkolnik E;Čelutkienė J;Zuozienė G;Butkuvienė I;Petrauskienė B;Šerpytis P;Laucevičius A;Lerman A
通讯作者：
Lerman A
DOI：
10.1161/atvbaha.110.211581
发表时间：
2010-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Heiss C;Schanz A;Amabile N;Jahn S;Chen Q;Wong ML;Rassaf T;Heinen Y;Cortese-Krott M;Grossman W;Yeghiazarians Y;Springer ML
通讯作者：
Springer ML
LncRNA WTAPP1 通过 MicroRNA 3120 和 Akt/PI3K/自噬途径通过 MMP1 促进内皮祖细胞的迁移和血管生成
影响因子：
5.2
作者：
Li, Wen-Dong;Zhou, Dong-Ming;Li, Xiao-Qiang
通讯作者：
Li, Xiao-Qiang
影响因子：
3.5
作者：
Ha, Chang Hoon;Kim, Sunghyen;Kwon, Kihwan
通讯作者：
Kwon, Kihwan
影响因子：
37.8
作者：
Benjamin, Emelia J.;Virani, Salim S.;Muntner, Paul
通讯作者：
Muntner, Paul