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Apoptosis

, Volume 23, Issue 7–8, pp 436–448 | Cite as

Protective effects of circulating microvesicles derived from ischemic preconditioning on myocardial ischemia/reperfusion injury in rats by inhibiting endoplasmic reticulum stress

  • Miao Liu
  • Yilu Wang
  • Qian Zhu
  • Junyu Zhao
  • Yao Wang
  • Man Shang
  • Minglin Liu
  • Yanna Wu
  • Junqiu Song
  • Yanxia Liu
Article
  • 196 Downloads

Abstract

Microvesicles (MVs) have been shown to be involved in pathophysiology of ischemic heart diseases. However, the underlying mechanisms are still unclear. Here we investigated the effects of MVs derived from ischemic preconditioning (IPC-MVs) on myocardial ischemic/reperfusion (I/R) injury in rats. Myocardial IPC model was elicited by three cycles of ischemia and reperfusion of the left anterior descending (LAD) coronary artery. IPC-MVs from the peripheral blood of the above animal model were isolated by ultracentrifugation and characterized by flow cytometry and transmission electron microscopy. IPC-MVs were administered intravenously (7 mg/kg) at 5 min before reperfusion procedure in I/R injury model which was induced by 30-min ischemia and 120-min reperfusion of LAD in rats. We found that total IPC-MVs and different phenotypes, including platelet-derived MVs (PMVs), endothelial cell-derived MVs (EMVs), leucocyte-derived MVs and erythrocyte-derived MVs (RMVs) were all isolated which were identified membrane vesicles (< 1 µm) with corresponding antibody positive. The numbers of PMVs, EMVs and RMVs were significantly increased in circulation of IPC treated rats respectively. Additionally, treatment with IPC-MVs significantly alleviated damage of myocardium, and restored cardiac function of I/R injury rats, as evidenced by increased heart rate, and decreased the elevation of ST-segment. The size of myocardial infarction, lactate dehydrogenase activity, and the number of apoptotic cardiomyocytes were also reduced significantly with IPC-MVs treatment, coincident with the above function amelioration. Moreover, IPC-MVs decreased the activity of caspase 3, and the expression of endoplasmic reticulum stress (ERS) markers, GRP78, CHOP and caspase 12 indicating the involvement of ERS-specific apoptosis in I/R injury, and cardioprotective effects of IPC-MVs. In summary, our study demonstrated a novel mechanism of IPC in which circulating IPC-MVs could protect hearts from I/R injury in rats through attenuation of ERS-induced apoptosis. These findings provide new insight into therapeutic potential of IPC-induced MVs in cardioprotection against I/R injury.

Keywords

Microvesicles Myocardial ischemia/reperfusion Myocardial ischemic preconditioning Cardioprotection Apoptosis Endoplasmic reticulum stress 

Notes

Acknowledgements

This work was supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant Number 20101202110005); the National Natural Science Foundation of China (Grant Numbers 81102446, 81370422); the Natural Science Foundation of Tianjin City (Grant Number 11JCZDJC18300); the Science and Technology Development Fund of Tianjin Education Commission for Higher Education (Grant Number 20110106); and the National Key Basic Research Program of China (973 Program Grant Number 2011CB933100).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Miao Liu
    • 1
    • 2
  • Yilu Wang
    • 1
    • 3
  • Qian Zhu
    • 1
  • Junyu Zhao
    • 1
  • Yao Wang
    • 1
  • Man Shang
    • 1
  • Minglin Liu
    • 4
    • 5
    • 6
  • Yanna Wu
    • 1
  • Junqiu Song
    • 1
  • Yanxia Liu
    • 1
  1. 1.Department of Pharmacology, School of Basic Medical SciencesTianjin Medical UniversityTianjinChina
  2. 2.Department of PersonnelTianjin University of Traditional Chinese MedicineTianjinChina
  3. 3.Department of PharmacyTianjin Medical University General HospitalTianjinChina
  4. 4.Section of Endocrinology, Diabetes and Metabolism, Department of MedicineTemple University School of MedicinePhiladelphiaUSA
  5. 5.Department of Dermatology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  6. 6.Philadelphia VA Medical CenterPhiladelphiaUSA

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