Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

Lijuan Chen; Yingjie Wang; Yaohua Pan; Lan Zhang; Chengxing Shen; Gangjian Qin; Muhammad Ashraf; Neal Weintraub; Genshan Ma; Yaoliang Tang

doi:10.1016/j.bbrc.2013.01.015

Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

Lijuan Chen, Yingjie Wang, Yaohua Pan, Lan Zhang, Chengxing Shen, Gangjian Qin, Muhammad Ashraf, Neal Weintraub, Genshan Ma, Yaoliang Tang^*

^*Corresponding author for this work

Medicine, Cardiology Division

Research output: Contribution to journal › Article › peer-review

317 Scopus citations

Abstract

Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12. h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation in vitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (. p<. 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

Original language	English (US)
Pages (from-to)	566-571
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	431
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2013.01.015
State	Published - Feb 15 2013

Funding

This work was supported by the American Heart Association Beginning Grant-in-Aid 0765094Y (to Y.T.); NIH grant HL086555 (to Y.T.), and NIH grants HL076684 and HL62984 (to N.L.W.) National Natural Science Foundation of China (No. 81270203, to L.C.).

Keywords

Apoptosis
Cardiac progenitors
Exosomes
Ischemia/reperfusion
MicroRNA

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2013.01.015

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title = "Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury",

abstract = "Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12. h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation in vitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (. p<. 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.",

keywords = "Apoptosis, Cardiac progenitors, Exosomes, Ischemia/reperfusion, MicroRNA",

author = "Lijuan Chen and Yingjie Wang and Yaohua Pan and Lan Zhang and Chengxing Shen and Gangjian Qin and Muhammad Ashraf and Neal Weintraub and Genshan Ma and Yaoliang Tang",

note = "Funding Information: This work was supported by the American Heart Association Beginning Grant-in-Aid 0765094Y (to Y.T.); NIH grant HL086555 (to Y.T.), and NIH grants HL076684 and HL62984 (to N.L.W.) National Natural Science Foundation of China (No. 81270203, to L.C.). ",

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doi = "10.1016/j.bbrc.2013.01.015",

language = "English (US)",

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pages = "566--571",

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T1 - Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

AU - Chen, Lijuan

AU - Wang, Yingjie

AU - Pan, Yaohua

AU - Zhang, Lan

AU - Shen, Chengxing

AU - Qin, Gangjian

AU - Ashraf, Muhammad

AU - Weintraub, Neal

AU - Ma, Genshan

AU - Tang, Yaoliang

N1 - Funding Information: This work was supported by the American Heart Association Beginning Grant-in-Aid 0765094Y (to Y.T.); NIH grant HL086555 (to Y.T.), and NIH grants HL076684 and HL62984 (to N.L.W.) National Natural Science Foundation of China (No. 81270203, to L.C.).

PY - 2013/2/15

Y1 - 2013/2/15

N2 - Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12. h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation in vitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (. p<. 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

AB - Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12. h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation in vitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (. p<. 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

KW - Apoptosis

KW - Cardiac progenitors

KW - Exosomes

KW - Ischemia/reperfusion

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Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

Abstract

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Keywords

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