Myofibroblast-Derived Exosome Induce Cardiac Endothelial Cell Dysfunction.
Myofibroblast-Derived Exosome Induce Cardiac Endothelial Cell Dysfunction.
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DOI：
10.3389/fcvm.2021.676267
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发表时间：
2021
影响因子：
3.6
通讯作者：
Verma SK
中科院分区：
文献类型：
--
作者：
Ranjan P;Kumari R;Goswami SK;Li J;Pal H;Suleiman Z;Cheng Z;Krishnamurthy P;Kishore R;Verma SK
背景：血管内皮细胞(ECs)在维持血管内环境稳定和心脏功能方面发挥着重要作用。研究表明，激活的成纤维细胞来源的外切体损害了肥厚心脏的心肌细胞功能，但其对内皮细胞的影响尚不清楚。因此，我们假设活化的心脏成纤维细胞来源的外切体(FB-Exo)介导内皮细胞功能障碍，因此FB-Exosomal含量的调节可能改善内皮功能。方法和结果：从心脏成纤维细胞(FB)条件培养液中分离得到外切体，并用纳米颗粒示踪分析和电子显微镜对其进行表征。从小鼠心脏中分离出内皮细胞。用从FB条件培养液中分离的外切体处理内皮细胞，再用转化生长因子-β-1(β-FB-Exo)或磷酸盐(对照组)处理FB。转化生长因子-β-1显著激活成纤维细胞，表现为胶原-1-α-1(COL-1-α-1)、骨膜蛋白(P-STN)和纤维连接蛋白(FN-1)基因表达增加，Smad2/3和p38磷酸化增加。血管内皮细胞功能受损(表现为血管内皮生长因子A、HIF1α、CD31和血管生成素1基因表达降低，管状形成和细胞迁移减少)，β-FB-Exo处理细胞。此外，转化生长因子-β1-FB-Exo处理的内皮细胞与对照细胞相比，细胞增殖减少，细胞凋亡率增加。转化生长因子-β1-FB-Exo Cargo分析显示纤维化相关miRNAs发生改变，包括miR-200A-3p水平显著升高。有趣的是，miR-200A-3p抑制活化的FBS，减轻转化生长因子-β1-FB-Exo介导的内皮功能障碍。结论：综上所述，本研究证实了激活的成纤维细胞来源的外切体中富含miR-200A-3p对内皮细胞生物学和功能的重要作用。
Background: Endothelial cells (ECs) play a critical role in the maintenance of vascular homeostasis and in heart function. It was shown that activated fibroblast-derived exosomes impair cardiomyocyte function in hypertrophic heart, but their effect on ECs is not yet clear. Thus, we hypothesized that activated cardiac fibroblast-derived exosomes (FB-Exo) mediate EC dysfunction, and therefore modulation of FB-exosomal contents may improve endothelial function. Methods and Results: Exosomes were isolated from cardiac fibroblast (FB)-conditioned media and characterized by nanoparticle tracking analysis and electron microscopy. ECs were isolated from mouse heart. ECs were treated with exosomes isolated from FB-conditioned media, following FB culture with TGF-β1 (TGF-β1-FB-Exo) or PBS (control) treatment. TGF-β1 significantly activated fibroblasts as shown by increase in collagen type1 α1 (COL1α1), periostin (POSTN), and fibronectin (FN1) gene expression and increase in Smad2/3 and p38 phosphorylation. Impaired endothelial cell function (as characterized by a decrease in tube formation and cell migration along with reduced VEGF-A, Hif1α, CD31, and angiopoietin1 gene expression) was observed in TGF-β1-FB-Exo treated cells. Furthermore, TGF-β1-FB-Exo treated ECs showed reduced cell proliferation and increased apoptosis as compared to control cells. TGF-β1-FB-Exo cargo analysis revealed an alteration in fibrosis-associated miRNAs, including a significant increase in miR-200a-3p level. Interestingly, miR-200a-3p inhibition in activated FBs, alleviated TGF-β1-FB-Exo-mediated endothelial dysfunction. Conclusions: Taken together, this study demonstrates an important role of miR-200a-3p enriched within activated fibroblast-derived exosomes on endothelial cell biology and function.
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影响因子：
5.6
作者：
Berthod, F;Germain, L;Auger, FA
通讯作者：
Auger, FA
影响因子：
21.3
作者：
Hergenreider, Eduard;Heydt, Susanne;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
内皮细胞，成纤维细胞和血管炎。
DOI：
10.1093/rheumatology/keh542
发表时间：
2005-07
期刊：
Rheumatology (Oxford, England)
影响因子：
--
作者：
Buckley CD;Rainger GE;Nash GB;Raza K
通讯作者：
Raza K
影响因子：
20.1
作者：
Accornero, Federica;van Berlo, Jop H.;Molkentin, Jeffery D.
通讯作者：
Molkentin, Jeffery D.
影响因子：
3.7
作者：
Hunter, Melissa Piper;Ismail, Noura;Zhang, Xiaoli;Aguda, Baltazar D.;Lee, Eun Joo;Yu, Lianbo;Xiao, Tao;Schafer, Jeffrey;Lee, Mei-Ling Ting;Schmittgen, Thomas D.;Nana-Sinkam, S. Patrick;Jarjoura, David;Marsh, Clay B.
通讯作者：
Marsh, Clay B.