期刊
FRONTIERS IN CARDIOVASCULAR MEDICINE
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcvm.2021.676267
关键词
cardiac fibrosis; angiogenesis; microRNA; exosome (vesicle); endothelial (dys)function
资金
- National Institutes of Health [HL135060]
- American Heart Association [14SDG20480104, 826859]
This study highlights the crucial role of miR-200a-3p enriched in activated fibroblast-derived exosomes in regulating endothelial cell biology and function.
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-beta 1 (TGF-beta 1-FB-Exo) or PBS (control) treatment. TGF-beta 1 significantly activated fibroblasts as shown by increase in collagen type1 alpha 1 (COL1 alpha 1), 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, Hif1 alpha, CD31, and angiopoietin1 gene expression) was observed in TGF-beta 1-FB-Exo treated cells. Furthermore, TGF-beta 1-FB-Exo treated ECs showed reduced cell proliferation and increased apoptosis as compared to control cells. TGF-beta 1-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-beta 1-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据