Oncotarget

Research Papers:

Protective effects of circulating microvesicles derived from myocardial ischemic rats on apoptosis of cardiomyocytes in myocardial ischemia/reperfusion injury

Yao Wang, Su Wei, Yi-Lu Wang, Miao Liu, Man Shang, Qi Zhang, Yan-Na Wu, Ming-Lin Liu, Jun-Qiu Song and Yan-Xia Liu _

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Oncotarget. 2017; 8:54572-54582. https://doi.org/10.18632/oncotarget.17424

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Abstract

Yao Wang1, Su Wei1, Yi-Lu Wang1, Miao Liu1, Man Shang1, Qi Zhang4, Yan-Na Wu1, Ming-Lin Liu2,3, Jun-Qiu Song1 and Yan-Xia Liu1

1Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China

2Section of Endocrinology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA19140, USA

3Section of Endocrinology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA

4Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

Correspondence to:

Yan-Xia Liu, email: [email protected]

Jun-Qiu Song, email: [email protected]

Keywords: microvesicles, ischemia/reperfusion, apoptosis, Bcl-2/Bax, GRP78

Received: October 17, 2016     Accepted: March 28, 2017     Published: April 26, 2017

ABSTRACT

Objective: To investigate the effects of circulating microvesicles derived from myocardial ischemia (I-MVs) on apoptosis in myocardial ischemia/reperfusion (I/R) injury in rats.

Methods: I-MVs from rats undergoing myocardial left anterior descending (LAD) coronary artery ligation were isolated by ultracentrifugation from circulating blood and characterized by flow cytometry. I-MVs were administered intravenously (4.8 mg/kg) at 5 min before reperfusion procedure in I/R injury model which was induced by 30-min of ischemia and 120-min of reperfusion of LAD in rats.

Results: Treatment with I-MVssignificantly reduced the size of myocardial infarction, the activities of serum CK-MB and LDH, and the number of apoptotic cardiomyocytes. The activities of caspase 3, caspase 9 and caspase 12 in myocardium were also decreased significantly with I-MVs treatment. Moreover, the expression of Bax was decreased but Bcl-2 was increased. The expression of glucose regulated protein 78 (GRP78), sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2) and phosphorylated phospholamban (p-PLB) were increased after being treated with I-MVs.

Conclusion: I-MVs could protect hearts from I/R injury in rats through SERCA2 and p-PLB of calcium regulatory proteins to alleviate intrinsic myocardial apoptosis including mitochondrial and endoplasmic reticulum pathways.


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