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A Selective TRPC3 Inhibitor Pyr3 Attenuates Myocardial Ischemia/Reperfusion Injury in Mice

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Summary

An emerging body of evidence indicates that transient receptor potential TRP channels act as important mediators for a wide variety of physiological functions and are potential targets for drug discovery. Our previous study has identified transient receptor potential channel 3 (TRPC3) and TRPC6 as cation channels through which most of the damaging calcium enters, aggravates pathological changes in vivo and increases ischemia/reperfusion (I/R) injury in mice. This study aimed to verify the effects of TRPC3 inhibitor Pyr3 on myocardial I/R injury in mice. C57BL/6J wild-type male mice (8 to 12 weeks old) were anesthetized with 3.3% chloral hydrate. A murine I (30 min)/R (24 h) injury model was established by temporary occlusion of the left anterior descending (LAD) coronary artery. Pyr3 was administered at concentrations of 0, 2.5, 5, or 10 mg/kg via the right jugular vein 5 min before reperfusion. We observed that the selective TRPC3 inhibitor, 10 mg/kg Pyr3, significantly decreased the infarct size of left ventricle, and reduced the myocardial cell apoptosis rate and inflammatory response in mice. In a conclusion, TRPC3 can function as a candidate target for I/R injury prevention, and Pyr3 may directly bind to TRPC3 channel protein, inhibit TRPC3 channel activity, and improve TRPC3-related myocardial I/R injury. Pyr3 may be used for clarification of TRPC3 functions and for treatments of TRPC3-mediated diseases.

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Author notes

  1. The authors contributed equally to this work.

Authors and Affiliations

  1. Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, Hubei, 442000, China

    Min Lu, Dan-dan Shi, Rui Liu, Yan Ding, Qiu-fang Zhang, Han-qin Wang, Jun-ming Tang & Xi-ju He

  2. Department of Neurology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, China

    Xiao-xia Fang

  3. Department of Ultrasound, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, China

    Xi-ju He

Authors
  1. Min Lu
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  2. Xiao-xia Fang
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  3. Dan-dan Shi
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  4. Rui Liu
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  5. Yan Ding
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  6. Qiu-fang Zhang
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  7. Han-qin Wang
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  8. Jun-ming Tang
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  9. Xi-ju He
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Corresponding author

Correspondence to Xi-ju He.

Additional information

This study was supported by grants from the National Natural Science Foundation of China (No. 81800266) and Cultivating Project for Young Scholars at Hubei University of Medicine (No. 2017QDJZR04 and No. 2018QDJZR10).

Conflict of Interest Statement

The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work.

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Lu, M., Fang, Xx., Shi, Dd. et al. A Selective TRPC3 Inhibitor Pyr3 Attenuates Myocardial Ischemia/Reperfusion Injury in Mice. CURR MED SCI 40, 1107–1113 (2020). https://doi.org/10.1007/s11596-020-2293-y

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  • DOI: https://doi.org/10.1007/s11596-020-2293-y

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