[1]姚思雨 张婷婷 安松涛.过表达miR-486-5p的骨髓间充质干细胞通过外泌体来保护缺氧损伤心肌细胞[J].心血管病学进展,2024,(9):858.[doi:10.16806/j.cnki.issn.1004-3934.2024.09.019]
　YAO Siyu,ZHANG Tingting,AN Songtao.Bone Marrow Mesenchymal Stem Cell Overexpressing miR-486-5p Protect Hypoxic-Injured Cardiomyocytes Via Exosomes[J].Advances in Cardiovascular Diseases,2024,(9):858.[doi:10.16806/j.cnki.issn.1004-3934.2024.09.019]
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过表达miR-486-5p的骨髓间充质干细胞通过外泌体来保护缺氧损伤心肌细胞()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2024年9期
页码:
858
栏目:
论著
出版日期:
2024-09-25

文章信息/Info

Title:
Bone Marrow Mesenchymal Stem Cell Overexpressing miR-486-5p Protect Hypoxic-Injured Cardiomyocytes Via Exosomes
作者:
姚思雨1 张婷婷2 安松涛1
(1. 郑州大学华中阜外医院,河南 郑州 450003;2. 河南省人民医院临床单细胞生物医学中心,河南 郑州 450003)
Author(s):
YAO Siyu1; ZHANG Tingting2; AN Songtao1
(1. Department of Cardiology,Central China Fuwai Hospital of Zhengzhou University,Zhengzhou 450003,Henan,China; 2. Center for Clinical Single-Cell Biomedicine,Henan Provincial People’s Hospital,People’s Hospital of Zhengzhou University,Zhengzhou 450003,Henan,China)
关键词:
骨髓间充质干细胞; 外泌体; 心肌缺氧; miR-486-5p; 凋亡
Keywords:
Bone marrow mesenchymal stem cell; Exosome; Myocardial hypoxia; miR-486-5p; Apoptosis
DOI:
10.16806/j.cnki.issn.1004-3934.2024.09.019
摘要:
目的 探讨过表达miR-486-5p小鼠骨髓间充质干细胞（BMSC）来源外泌体（Exo）对缺氧损伤心肌细胞的影响及机制。方法 通过慢病毒转染来构建过表达miR-486-5p的小鼠BMSC。提取转染成功的BMSC所分泌的Exo，包括空载体BMSC分泌的Exo（Exo-NC）、miR-486-5p过表达BMSC分泌的Exo（Exo-miR-486）及未处理BMSC分泌的Exo（Exo-Control）。取12～18 d 胎鼠原代心肌细胞，将其分为常氧培养组（Normoxia组）、缺氧培养组（Hypoxia组）、Hypoxia＋Exo-NC组及Hypoxia＋Exo-miR-486组，并给予不同时间的缺氧处理来模拟心肌细胞缺氧状态，检测细胞增殖状态、凋亡率，以及活性氧（ROS）、NOD样受体热蛋白结构域相关蛋白3（NLRP3）和裂解的胱天蛋白酶-1（Cleaved caspase-1） 的表达水平。结果 Hypoxia组心肌细胞增殖能力低于Normoxia组，而凋亡率及ROS、NLRP3和Cleaved caspase-1的表达水平均高于Normoxia组（P＜0.05）；Hypoxia＋Exo-NC组心肌细胞增殖能力高于Hypoxia组，凋亡率及ROS、NLRP3和Cleaved caspase-1的表达水平低于Hypoxia组（P＜0.05）；Hypoxia＋Exo-miR-486组心肌细胞增殖能力高于Hypoxia＋Exo-NC组，凋亡率及ROS、NLRP3和Cleaved caspase-1表达水平 低于Hypoxia＋Exo-NC组（P＜0.05）。结论 来自miR-486-5p过表达BMSC的Exo能减少缺氧导致的ROS的产生及其引起的心肌细胞的凋亡，并改善缺氧引起的心肌细胞增殖缓慢的问题。
Abstract:
Objective To investigate the effects and mechanisms of exosomes derived from bone marrow mesenchymal stem cell(BMSC) in mouse overexpressing miR-486-5p on hypoxic -injured cardiomyocytes. Methods Mouse BMSC overexpressing miR-486-5p were constructed by lentivirus transfection. Exosomes(Exo) secreted by successfully transfected BMSC were extracted ,including Exo secreted by empty carrier BMSC(Exo-NC),Exo secreted by BMSC overexpressing miR-486-5p (Exo-miR-486) ,and Exo secreted by untreated BMSC(Exo-Control). Primary cardiomyocytes from 12～18 days old fetal rats were divided into normal oxygen culture group(Normoxia group),hypoxia culture group(Hypoxia group),Hypoxia+Exo-NC group and Hypoxia+Exo-miR-486 group,and were given hypoxia treatments for different times to stimulate the hypoxic state of cardiomyocytes,and cell proliferation,apoptosis rate,and the expression levels of reactive oxygen species(ROS), NOD-like receptor thermal protein domain associated protein 3(NLRP3),and Cleaved caspase-1 were examined. Results The proliferation of cardiomyocytes in Hypoxia group was lower than that in Normoxia group ,while the apoptosis rate and the expression levels of ROS,NLRP3 and Cleaved caspase-1 in Hypoxia group were higher than those in Normoxia group( P＜0.05); Myocardial c ell proliferation capacity in Hypoxia+Exo-NC group was higher than that in Hypoxia group,apoptosis rate and expression levels of ROS,NLRP3 and Cleaved caspase-1 were lower than those in Hypoxia group( P＜0.05); The proliferation ability of myocardial cells in Hypoxia+Exo-miR-486 group was higher than that in Hypoxia+Exo-NC group,and the apoptosis rate and the expression levels of ROS,NLRP3 and Cleaved caspase-1 were lower than those in Hypoxia+Exo-NC group( P＜0.05). Conclusion Exosomes from BMSC overexpressed with miR-486-5p can reduce hypoxic-induced ROS production and apoptosis of cardiomyocytes ,and ameliorate hypoxic-induced slow proliferation of cardiomyocytes

参考文献/References:

[1] Zhang H,Zhao C,Jiang G,et al. Apelin rejuvenates aged human mesenchymal stem cells by regulating autophagy and improves cardiac protection after infarction[J]. Front Cell Dev Biol,2021,9:628463.

[2] Matta A,Nader V,Lebrin M,et al. Pre-conditioning methods and novel approaches with mesenchymal stem cells therapy in cardiovascular disease[J]. Cells,2022,11(10):1620.

[3] Han Y,Li X,Zhang Y,et al. Mesenchymal stem cells for regenerative medicine[J]. Cells,2019,8(8):886.

[4] Zou Y,Li L,Li Y,et al. Restoring cardiac functions after myocardial infarction-ischemia/reperfusion via an exosome anchoring conductive hydrogel[J]. ACS Appl Mater Interfaces,2021,13(48):56892-56908.

[5] Sahoo S,Adamiak M,Mathiyalagan P,et al. Therapeutic and diagnostic translation of extracellular vesicles in cardiovascular diseases: roadmap to the clinic[J]. Circulation,2021,143(14):1426-1449.

[6] 叶莎,杨翠玲,郑媛媛. 骨髓间充质干细胞来源外泌体通过PI3K/Akt途径减轻过氧化氢诱导心肌细胞损伤[J]. 心血管病学进展,2022,43(3):269-273.

[7] Zhan C,Liu K,Zhang Y,et al. Myocardial infarction unveiled: key miRNA players screened by a novel lncRNA-miRNA-mRNA network model[J]. Comput Biol Med,2023,160:106987.

[8] Mompeón A,Pérez-Cremades D,Paes A B,et al. Circulating miRNA fingerprint and endothelial function in myocardial infarction: comparison at acute event and one-year follow-up[J]. Cells,2022,11(11):1823.

[9] Li Q,Xu Y,Lv K,et al. Small extracellular vesicles containing miR-486-5p promote angiogenesis after myocardial infarction in mice and nonhuman primates[J]. Sci Transl Med,2021,13(584): eabb0202.

[10] Wang H,Fan M,An Y,et al. Molecular mechanism of long noncoding RNA SNHG14 in osteogenic differentiation of bone marrow-derived mesenchymal stem cells through the NEDD4L/FOXA2/PCP4 axis[J]. Stem Cells Int,2023,2023:7545635.

[11] 苏未,张颖,马爽. 1990—2019年中国和全球缺血性心脏病疾病负担变化趋势与发病预测分析[J]. 中国全科医学,2024,27 (19):2375-2381.

[12] Yi F,Xiao H,Song M,et al. BMSC-derived exosomal miR-148b-3p attenuates OGD/R-induced HMC3 cell activation by targeting DLL4 and Notch1[J]. Neurosci Res,2024,199:36-47.

[13] Liu S C,Cao Y H,Chen L B,et al. BMSC-derived exosomal lncRNA PTENP1 suppresses the malignant phenotypes of bladder cancer by upregulating SCARA5 expression[J]. Cancer Biol Ther,2022,23(1):1-13.

[14] Liu Y,Guo Y,Bao S,et al. Bone marrow mesenchymal stem cell-derived exosomal microRNA-381-3p alleviates vascular calcification in chronic kidney disease by targeting NFAT5 [J]. Cell Death Dis,2022,13(3):278.

[15] Han C,Yang J,Sun J,et al. Extracellular vesicles in cardiovascular disease: biological functions and therapeutic implications[J]. Pharmacol Ther,2022,233:108025.

[16] Heo J,Kang H. Exosome-based treatment for atherosclerosis[J]. Int J Mol Sci,2022,23(2):1002.

[17] Cai Y,Li Y. Upregulation of miR-29b-3p protects cardiomyocytes from hypoxia-induced apoptosis by targeting TRAF5[J]. Cell Mol Biol Lett,2019,24:27.

[18] Sun Y,Su Q,Li L,et al. MiR-486 regulates cardiomyocyte apoptosis by p53-mediated BCL-2 associated mitochondrial apoptotic pathway[J]. BMC Cardiovasc Disord,2017,17(1):119.

[19] Zhang Z,Yang J,Yan W,et al. Pretreatment of cardiac stem cells with exosomes derived from mesenchymal stem cells enhances myocardial repair[J]. J Am Heart Assoc,2016,5(1):e002856.

[20] Morales C R,Pedrozo Z,Lavandero S,et al. Oxidative stress and autophagy in cardiovascular homeostasis[J]. Antioxid Redox Signal,2014,20(3):507-518.

[21] Songbo M,Lang H,Xinyong C,et al. Oxidative stress injury in doxorubicin-induced cardiotoxicity[J]. Toxicol Lett,2019,307:41-48.

[22] Wei S,Ma W,Li X,et al. Involvement of ROS/NLRP3 inflammasome signaling pathway in doxorubicin-induced cardiotoxicity[J]. Cardiovasc Toxicol,2020,20(5):507-519.

[23] Rabinovich-Nikitin I,Rasouli M,Reitz CJ,et al. Mitochondrial autophagy and cell survival is regulated by the circadian Clock gene in cardiac myocytes during ischemic stress[J]. Autophagy,2021,17(11):3794-3812.

[24] He Y,Hara H,Nú?ez G. Mechanism and regulation of NLRP3 inflammasome activation[J]. Trends Biochem Sci,2016,41(12):1012-1021.

[25] Huang Y,Xu W,Zhou R. NLRP3 inflammasome activation and cell death[J]. Cell Mol Immunol,2021,18(9):2114-2127.

[26] Liu D,Zeng X,Li X,et al. Role of NLRP3 inflammasome in the pathogenesis of cardiovascular diseases[J]. Basic Res Cardiol,2018,113(1):5.

[27] Peng J F,Zhao X N,Zhang M,et al. Punicalagin attenuates ventricular remodeling after acute myocardial infarction via regulating the NLRP3/caspase-1 pathway[J]. Pharm Biol,2023,61(1):963-972.

[28] Jin Y,Fu J. Novel insights into the NLRP 3 inflammasome in atherosclerosis[J]. J Am Heart Assoc,2019,8(12): e012219.

[29] Zhao H,Gu Y,Chen H. Propofol ameliorates endotoxin?induced myocardial cell injury by inhibiting inflammation and apoptosis via the PPARγ/HMGB1/NLRP3 axis[J]. Mol Med Rep,2021,23(3):176.

[30] Wang SH,Cui LG,Su XL,et al. GSK-3β-mediated activation of NLRP3 inflammasome leads to pyroptosis and apoptosis of rat cardiomyocytes and fibroblasts[J]. Eur J Pharmacol,2022,920:174830.

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更新日期/Last Update: 2024-10-17