Ozone protects cardiomyocytes against ischemia/reperfusion injury: Regulating the heat shock protein 70 (HSP70) expression through activating the JAK2/STAT3 Pathway

ABSTRACT

Ischemia/reperfusion (I/R) injury causes complications in early coronary artery reperfusion for acute myocardial infarction (AMI). Ozone (O₃) has been reported to be applied for protecting I/R injury, but its detailed mechanism remains unclear. Our study focused on the protective effect of O₃ pretreatment on myocardial I/R injury and JAK2/STAT3 signaling and HSP70 regulation involving in the mediation. The rat hearts which were perfused and isolated as well as the cultured cardiomyocytes of neonatal rat were exposed to hypoxia/reoxygenation (H/R) and different concentrations of O₃ followed by heat shock protein 70 (HSP70) siRNA treatment. The results showed O₃ attenuated the suppression of cell viability induced by H/R and decreased the release of activity of creatine kinase (CK), lactate dehydrogenase (LDH) and apoptosis of cardiomyocytes in vitro. Moreover, O₃ also activated the JAK2/STAT3 signaling, upregulated the expression of HSP70 both in vitro and vivo, and decreased the index of apoptosis of cardiomyocytes caused by I/R as well as myocardial infarct area in vivo. In addition, HSP70 siRNA and JAK2 inhibitor AG490 inhibited the cardioprotective effect of O₃. And the expression of HSP70 increased by ozone was reduced by AG-490. In conclusion, our results demonstrated that ozone protects cardiomyocytes in I/R injury through regulation of the expression of HSP70 by activating the JAK2/STAT3 pathway.

KEYWORDS:

• Ozone
• ischemia/reperfusion injury
• JAK2/STAT3
• HSP70
• myocardial infarction

Highlights

• Ozone attenuates the suppression of cell viability induced by hypoxia/reoxygenation (H/R).

• Ozone decreases the release of activity of CK, LDH and apoptosis of cardiomyocytes.

• Ozone protects cardiomyocytes in I/R injury through regulation of the expression of HSP70 by activating the JAK2/STAT3 pathway.

Abbreviations

Acute myocardial infarction: AMI

Cell Counting Kit-8: CCK8

Creatine kinase: CK

Heat shock protein 70: HSP70

Hypoxia/reoxygenation: H/R

Ischemia/reperfusion: I/R

Janus kinase 2: JAK2

Lactate dehydrogenase: LDH

Left anterior descending: LAD

Signal transduction and activator of transcription 3: STAT3

Triphenyltetrazolium chloride: TTC

Acknowledgements

The authors grateful acknowledge the helpful comments from copyeditors of TopEdit which greatly improved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

Supported by a grant from the Guangzhou Panyu District Science and Technology and Information Bureau Fund project (No.2018-Z04-48).