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Effect of the Kv1.3 voltage-gated potassium channel blocker PAP-1 on the initiation and progress of atherosclerosis in a rat model

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Abstract

Acute coronary syndrome is a serious medical emergency. It occurs when an atherosclerotic plaque ruptures, leading to thrombus formation within a coronary artery. Previous studies have shown that T cells are involved in the initiation and progression of acute coronary syndrome. CD4+CD28null T lymphocytes increase in atherosclerotic plaque, and voltage-gated potassium channel Kv1.3 blockers can suppress the function of these cells in vitro by preventing exocytosis of their cytoplasmic granules. The purpose of this study was to investigate the effect of PAP-1, a small molecule voltage-gated potassium channel Kv1.3 blocker, on the development of atherosclerosis (AS) in a rat model and the potential mechanism for this effect. Plasma lipids, interferonγ, CRP, CD4+CD28null T cells, and perforin were increased and unstable atherosclerotic plaques developed in the rat model of AS. Blockade of the Kv1.3 potassium channel via PAP-1 administration decreased perforin levels and prevented plaque formation but had no effect on the other changes seen in this AS model. These findings suggest that the small molecule, voltage-gated potassium channel Kv1.3 blocker PAP-1 can suppress the development of AS in a rat model, most likely by inhibiting the exocytosis of cytoplasmic granules from CD4+CD28null T cells.

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Acknowledgments

This project was supported by grants from the National Natural Sciences Foundation of China (No. 30871070) and Natural Sciences Foundation of Hubei Province (No. 20604002—258). We are deeply indebted to Dr. H. Wulff (Department of Pharmacology, UC Davis) for providing PAP-1 and for her critical reading of the manuscript and valuable suggestions.

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None of the authors has any conflict of interest pertaining to this article.

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Authors and Affiliations

  1. Department of Gerontology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Xiaofen Wu, Rende Xu, Ming Cao, Lei Ruan, Xingfen Wang & Cuntai Zhang

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  1. Xiaofen Wu
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  2. Rende Xu
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  3. Ming Cao
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  4. Lei Ruan
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  5. Xingfen Wang
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  6. Cuntai Zhang
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Correspondence to Cuntai Zhang.

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Wu, X., Xu, R., Cao, M. et al. Effect of the Kv1.3 voltage-gated potassium channel blocker PAP-1 on the initiation and progress of atherosclerosis in a rat model. Heart Vessels 30, 108–114 (2015). https://doi.org/10.1007/s00380-013-0462-7

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  • DOI: https://doi.org/10.1007/s00380-013-0462-7

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