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 | |
| State | Published - Feb 15 2013 |
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Keywords
- Apoptosis
- Cardiac progenitors
- Exosomes
- Ischemia/reperfusion
- MicroRNA
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury. / Chen, Lijuan; Wang, Yingjie; Pan, Yaohua; Zhang, Lan; Shen, Chengxing; Qin, Gangjian; Ashraf, Muhammad; Weintraub, Neal; Ma, Genshan; Tang, Yaoliang.
In: Biochemical and Biophysical Research Communications, Vol. 431, No. 3, 15.02.2013, p. 566-571.Research output: Contribution to journal › Article
}
TY - JOUR
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
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
KW - MicroRNA
UR - http://www.scopus.com/inward/record.url?scp=84873713781&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84873713781&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2013.01.015
DO - 10.1016/j.bbrc.2013.01.015
M3 - Article
C2 - 23318173
AN - SCOPUS:84873713781
VL - 431
SP - 566
EP - 571
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -