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Valsartan preconditioning protects against myocardial ischemia–reperfusion injury through TLR4/NF-κB signaling pathway

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Abstract

Toll-like receptor 4 (TLR4) activation has been implicated in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. The activated TLR4 is capable of activating a variety of proinflammatory mediators, such as tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6). Valsartan as a kind of Angiotensin II type 1 receptor blockers is gradually used for the treatment of ischemic heart disease depending on its anti-inflammation function. Therefore, we hypothesized that valsartan protects against myocardial I/R injury by suppressing TLR4 activation. We constructed the rat model of myocardial I/R injury. The rats were pretreated with valsartan for 2 weeks, and then subjected to 30 min ischemia and 2 h reperfusion. TLR4 and Nuclear factor kappa-B (NF-κB) levels were detected by quantitative real-time PCR and western blot. In order to evaluate myocardial damage, the myocardial infarct size, histopathologic changes, and the release of myocardial enzymes, proinflammation cytokines and Angiotensin II were analyzed by triphenyl tetrazolium chloride (TTC) staining, light microscopy, and enzyme-linked immunosorbent assay (ELISA), respectively. Valsartan preconditioning inhibited TLR4 and NF-κB expressions concomitant with an improvement in myocardial injury, such as smaller infarct size, fewer release of myocardial enzymes, and proinflammation mediators. These findings suggest that valsartan plays a pivotal role in the protective effects on myocardial I/R injury. This protection mechanism is possibly due to its anti-inflammation function via TLR4/NF-κB signaling pathway.

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Acknowledgment

We thank Jia-jun Wang from the Department of Immunology, Medical Science College of China Three Gorges University for his technical support and helpful suggestions on this study.

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Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China

    Jian Yang & Hong Jiang

  2. Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, 443000, China

    Jun Yang, Li-Hua Chen & Xiao-Dong Zhang

  3. Department of Cardiology, Yichang Central People’s Hospital, Yichang, Hubei, 443000, China

    Jia-Wang Ding & Song Li

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  1. Jian Yang
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Correspondence to Hong Jiang.

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Yang, J., Jiang, H., Yang, J. et al. Valsartan preconditioning protects against myocardial ischemia–reperfusion injury through TLR4/NF-κB signaling pathway. Mol Cell Biochem 330, 39–46 (2009). https://doi.org/10.1007/s11010-009-0098-1

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