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Anti-inflammatory Effect of B-Type Natriuretic Peptide Postconditioning During Myocardial Ischemia–Reperfusion: Involvement of PI3K/Akt Signaling Pathway

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ABSTRACT

High mobility group box 1 protein (HMGB1) plays an important role in myocardial ischemia–reperfusion (I/R) injury. B-type natriuretic peptide (BNP) postconditioning has been reported to reduce myocardial I/R injury. The present study investigated whether postconditioning of BNP could reduce myocardial I/R injury by inhibiting HMGB1 expression and the potential mechanisms in rats. The left anterior descending coronary arteries of rats were occluded to induce ischemia for 30 min and reopened to imitate reperfusion for 4 h. The rats were treated with BNP (0.03 μg/kg min, i.v.) 15 min before reperfusion until the end of the procedure, with or without treatment of LY294002 (an inhibitor of phosphoinositide 3-kinase (PI3K), 0.3 mg/kg, i.v.), which was injected 20 min before reperfusion. Lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and infarct size were measured. Phospho-Akt, total Akt, and HMGB1 expression were assessed by immunoblotting. The results showed that treatment of BNP postconditioning could significantly decrease the infarct size and the levels of LDH and CK after 4-h reperfusion (all p < 0.05). BNP postconditioning could also significantly inhibit the increases of TNF-α and IL-6 (both p < 0.05). In addition, BNP postconditioning could significantly inhibit HMGB1 expression induced by I/R (p < 0.05). Administration of LY294002 abolished the effects of BNP postconditioning on myocardial I/R injury and the expressions of phospho-Akt and HMGB1 (all p < 0.05). The present study suggests that postconditioning of BNP could protect against myocardial I/R injury which may be associated with inhibiting HMGB1 expression, while PI3K/Akt signaling pathway may be involved in the expression of HMGB1 and the protective effect of BNP postconditioning.

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ACKNOWLEDGMENTS

This study was supported by grants from the National Natural Science Foundation of China (Nos. 81100146 and 81370308), the Fundamental Research Funds for the Central Universities (No. 1210486083), the Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20110141120060), and the Fundamental Research Funds of Wuhan City (No. 2013070104010044).

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Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan City, 430060, China

    Gangying Hu, Xingyue Huang, Hong Jiang & Xiaorong Hu

  2. Cardiovascular Research Institute of Wuhan University, Wuhan, China

    Gangying Hu, Xingyue Huang, Hong Jiang & Xiaorong Hu

  3. Department of Cardiology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, China

    Kai Zhang & Xiaorong Hu

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  1. Gangying Hu
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  2. Xingyue Huang
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  4. Hong Jiang
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  5. Xiaorong Hu
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Correspondence to Xiaorong Hu.

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Hu, G., Huang, X., Zhang, K. et al. Anti-inflammatory Effect of B-Type Natriuretic Peptide Postconditioning During Myocardial Ischemia–Reperfusion: Involvement of PI3K/Akt Signaling Pathway. Inflammation 37, 1669–1674 (2014). https://doi.org/10.1007/s10753-014-9895-0

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