Tanshinone IIA enhances the therapeutic efficacy of mesenchymal stem cells derived exosomes in myocardial ischemia/reperfusion injury via up-regulating miR-223-5p

被引：44
作者：
Li, Sheng [1 ,2 ]
Yang, Ke [1 ,2 ]
Cao, Weilong [1 ,2 ]
Guo, Rui [1 ,2 ]
Liu, Zhihao [1 ,2 ]
Zhang, Jing [1 ,2 ]
Fan, Aodi [1 ,2 ]
Huang, Yuting [4 ]
Ma, Chuanrui [1 ]
Li, Lan [1 ,2 ]
Fan, Guanwei [1 ,2 ,3 ]
机构：
[1] Tianjin Univ Tradit Chinese Med, Natl Clin Res Ctr Chinese Med Acupuncture & Moxibu, State Key Lab Component based Chinese Med, Teaching Hosp 1, Tianjin, Peoples R China
[2] Tianjin Univ Tradit Chinese Med, State Key Lab Modern Chinese Med, Key Lab Pharmacol Tradit Chinese Med Formulae, Minist Educ, Tianjin, Peoples R China
[3] Huanggang Normal Univ, Hubei Key Lab Econ Forest Germplasm Improvement &, Huanggang, Peoples R China
[4] Gannan Med Univ, Affiliated Hosp 1, Key Lab Prevent & Treatment Cardiovasc & Cerebrova, Minist Educ, Ganzhou 341000, Peoples R China
来源：
JOURNAL OF CONTROLLED RELEASE | 2023年 / 358卷
关键词：
Exosomes; Tanshinone IIA; miR-223-5p; Myocardial ischemia reperfusion; Mesenchymal stem cell; ISCHEMIA REPERFUSION INJURY; DISEASE JACC MACROPHAGE; ANGIOGENESIS; SECRETION; PROTECTS; IMPROVE;
D O I：
10.1016/j.jconrel.2023.04.014
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Myocardial ischemia-reperfusion injury (MI/RI) is a serious obstacle for patients with coronary heart disease (CHD) to benefit from post-ischemic reflow. The low immunogenicity and low carcinogenicity of mesenchymal stem cells (MSCs)-derived exosomes (exo) offer advantage in treating myocardial injuries. Tanshinone IIA (TSA) is an effective drug for MI/RI treatment. However, the underlying mechanism and targets remain obscure. In this study, we systematically investigated the therapeutic effect and its mechanism of TSA-pretreated MSC-derived exosomes (TSA-MSCexo) in ameliorating MI/RI in rats. Expectedly, the MI/RI was significantly relieved by TSA-MSCexo compared with MSCexo. Moreover, the overexpression of CCR2 in rats' heart was used to determine CCR2 had a regulatory effect on monocyte infiltration and angiogenesis after MI/RI. MiRNA microarray analysis of MSCexo and TSA-MSCexo revealed miR-223-5p an effective candidate mediator for TSA-MSCexo to exert its car-dioprotective function and CCR2 as the downstream target. In summary, our findings indicated that miR-223-5p packaged in TSA-MSCexo inhibited CCR2 activation to reduce monocyte infiltration and enhanced angiogenesis to alleviate MI/RI. Thus, the development of cell free therapies for exosomes derived from the combination TSA and MSC provides an effective strategy for the clinical therapies of ischemic cardiomyopathy.
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收藏
页码：13 / 26
页数：14
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