Modification of Cardiac Progenitor Cell-Derived Exosomes by miR-322 Provides Protection against Myocardial Infarction through Nox2-Dependent Angiogenesis

被引:86
|
作者
Youn, Seock-Won [1 ]
Li, Yang [1 ]
Kim, Young-Mee [1 ]
Sudhahar, Varadarajan [1 ]
Abdelsaid, Kareem [1 ]
Kim, Ha Won [1 ]
Liu, Yutao [2 ]
Fulton, David J. R. [1 ,3 ]
Ashraf, Muhammad [1 ]
Tang, Yaoliang [1 ,4 ]
Fukai, Tohru [1 ,3 ,5 ]
Ushio-Fukai, Masuko [1 ,4 ]
机构
[1] Augusta Univ, Med Coll Georgia, Vasc Biol Ctr, Augusta, GA 30912 USA
[2] Augusta Univ, Dept Cellular Biol & Anat, Augusta, GA 30912 USA
[3] Augusta Univ, Dept Pharmacol & Toxicol, Augusta, GA 30912 USA
[4] Augusta Univ, Dept Med Cardiol, Augusta, GA 30912 USA
[5] Charlie Norwood Vet Affairs Med Ctr, Augusta, GA 30912 USA
关键词
cardiac progenitor cell; myocardial infarction; exosome; miR-322; reactive oxygen species; NADPH oxidase; angiogenesis; NADPH OXIDASE; ENDOTHELIAL-CELL; BONE-MARROW; EXTRACELLULAR VESICLES; STEM-CELLS; MIGRATION; MICRORNA; NOX4; PROLIFERATION; BIOGENESIS;
D O I
10.3390/antiox8010018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Myocardial infarction (MI) is the primary cause of cardiovascular mortality, and therapeutic strategies to prevent or mitigate the consequences of MI are a high priority. Cardiac progenitor cells (CPCs) have been used to treat cardiac injury post-MI, and despite poor engraftment, they have been shown to inhibit apoptosis and to promote angiogenesis through poorly understood paracrine effects. We previously reported that the direct injection of exosomes derived from CPCs (CPCexo) into mouse hearts provides protection against apoptosis in a model of acute ischemia/reperfusion injury. Moreover, we and others have reported that reactive oxygen species (ROS) derived from NADPH oxidase (NOX) can enhance angiogenesis in endothelial cells (ECs). Here we examined whether bioengineered CPCexo transfected with a pro-angiogenic miR-322 (CPCexo-322) can improve therapeutic efficacy in a mouse model of MI as compared to CPCexo. Systemic administration of CPCexo-322 in mice after ischemic injury provided greater protection post-MI than control CPCexo, in part, through enhanced angiogenesis in the border zones of infarcted hearts. Mechanistically, the treatment of cultured human ECs with CPCexo-322 resulted in a greater angiogenic response, as determined by increased EC migration and capillary tube formation via increased Nox2-derived ROS. Our study reveals that the engineering of CPCexo via microRNA (miR) programing can enhance angiogenesis, and this may be an effective therapeutic strategy for the treatment of ischemic cardiovascular diseases.
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页数:15
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