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Dynamic alterations of connexin43, matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 during ventricular fibrillation in canine

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Abstract

The aim of this study is to investigate the dynamic alterations of cardiac connexin 43 (Cx43), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the setting of different ventricular fibrillation (VF) duration. In this study, thirty-two dogs were randomly divided into sham control group, 8-min VF group, 12-min VF group, and 30-min VF group. Cx43 and phosphorylated Cx43 (p-Cx43) in tissues were detected by western blot and immunofluorescence analysis. MMP-2 and TIMP-2 were detected by western blot and immunohistochemistry analysis. The results showed that Cx43 levels in three VF groups were significantly decreased compared with sham control group. p-Cx43 levels in 12-min and 30-min VF groups were significantly reduced compared with sham control group. The ratio of p-Cx43/Cx43 was also decreased in VF groups. Compared with sham controls, no significant difference was observed between the sham control group and 8-min VF group in MMP-2 level, but MMP-2 level increased in 12-min and 30-min VF groups. The ratios of MMP-2/TIMP-2 were higher in VF groups, and were correlated with the duration of VF. A remarkable correlation was observed between the ratio of p-Cx43/Cx43 and MMP-2/TIMP-2 (r = −0.93, P < 0.01). In conclusion, the alteration of Cx43 and/or p-Cx43 levels and the imbalance of MMP-2 and TIMP-2 may contribute to the initiation and/or persistence of VF. Maneuvers managed to modulate Cx43 level or normalize the balance of MMP-2/TIMP-2 are promising to ameliorate prognosis of VF.

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Acknowledgments

This study was sponsored by the Natural Science Foundation of China (81270238) and supported by the Scientific Development Plan of Shandong Province of China (2012G0021850).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Jinan, 250012, Shandong, China

    Jing Wang, Jing-sha Li, Hong-zhen Liu, Shao-lei Yi, Guo-ying Su, Yun Zhang & Jing-quan Zhong

  2. Department of Cardiology, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, China

    Jing Wang, Jing-sha Li, Hong-zhen Liu, Shao-lei Yi, Guo-ying Su, Yun Zhang & Jing-quan Zhong

  3. Department of Keshan Disease, Shandong Provincial Institute for Endemic Diseases Control, Jinan, 250014, China

    Jing Wang

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  1. Jing Wang
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Correspondence to Jing-quan Zhong.

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Wang, J., Li, Js., Liu, Hz. et al. Dynamic alterations of connexin43, matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 during ventricular fibrillation in canine. Mol Cell Biochem 391, 259–266 (2014). https://doi.org/10.1007/s11010-014-2012-8

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  • DOI: https://doi.org/10.1007/s11010-014-2012-8

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