Human Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Alleviate Hypoxia-Induced Pulmonary Arterial Hypertension in Mice Via Macrophages

被引:3
|
作者
Liu, Hong [1 ,2 ,3 ,4 ]
Zhang, Qingqing [1 ,2 ,3 ,4 ,5 ]
Liu, Chuanchuan [5 ]
Zhang, Yuwei [6 ]
Wang, Yuxiang [1 ,2 ,3 ,4 ]
Huang, Pan [1 ,2 ,3 ,4 ]
Ma, Lan [1 ,2 ,3 ,4 ]
Ge, Rili [1 ,2 ,3 ,4 ]
机构
[1] Res Ctr High Altitude Med, Xining, Peoples R China
[2] Minist High Altitude Med, Key Lab, Xining, Peoples R China
[3] Qinghai Utah Joint Key Lab Plateau Med, Key Lab Appl Fundamentals High Altitude Med, Xining, Peoples R China
[4] Lab High Altitude Med Qinghai Prov, Xining, Peoples R China
[5] Qinghai Univ, Affiliated Hosp, Xining 810001, Qinghai, Peoples R China
[6] Qinghai Univ, Dept Publ Hlth, Xining, Peoples R China
基金
中国国家自然科学基金;
关键词
mesenchymal stromal cells; exosomes; immunomodulation; hypoxic pulmonary hypertension; pulmonary vascular remodeling; immune microenvironment; SMOOTH-MUSCLE-CELLS; STEM-CELLS; LUNG; RECRUITMENT; ACTIVATION; MICROVESICLES; INFLAMMATION;
D O I
10.1093/stmcls/sxad098
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Pulmonary hypertension (PH) is an intractable, severe, and progressive cardiopulmonary disease. Recent findings suggest that human umbilical cord mesenchymal stromal cells (HUCMSCs) and HUCMSC-derived exosomes (HUCMSC-Exos) possess potential therapeutic value for PH. However, whether they have beneficial effects on hypoxic pulmonary hypertension (HPH) is unclear. Exos are released into the extracellular environment by the fusion of intracellular multivesicular bodies with the cell membrane, and they play an important role in cellular communication. Exos ameliorate immune inflammation levels, alter macrophage phenotypes, regulate mitochondrial metabolic function, and inhibit pulmonary vascular remodeling, thereby improving PH. Macrophages are important sources of cytokines and other transmitters and can promote the release of cytokines, vasoactive molecules, and reactive oxygen species, all of which are associated with pulmonary vascular remodeling. Therefore, the aim of this study was to investigate whether HUCMSC-Exos could improve the lung inflammatory microenvironment and inhibit pulmonary vascular remodeling by targeting macrophages and identifying the underlying mechanisms. The results showed that HUCMSC-Exos promoted M2 macrophage polarization, decreased pro-inflammatory factors, increased IL-10 levels, and inhibited IL-33/ST2 axis expression, thereby inhibiting hypoxia-induced proliferation of pulmonary artery smooth muscle cells and ameliorating HPH. Graphical Abstract
引用
收藏
页码:329 / 345
页数:17
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