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The role of P2Y12 receptor in ischemic stroke of atherosclerotic origin

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Abstract

Atherosclerosis is a chronic and progressive disease of the arterial walls and a leading cause of non-cardioembolic ischemic stroke. P2Y12 is a well-recognized receptor that is expressed on platelets and is a target of thienopyridine-type antiplatelet drugs. In the last few decades, P2Y12 receptor inhibitors, such as clopidogrel, have been applied for the secondary prevention of non-cardioembolic ischemic stroke. Recent clinical studies have suggested that these P2Y12 receptor inhibitors may be more effective than other antiplatelet drugs in patients with ischemic stroke/transient ischemic attack of atherosclerotic origin. Moreover, animal studies have also shown that the P2Y12 receptor may participate in atherogenesis by promoting the proliferation and migration of vascular smooth muscle cells (VSMCs) and endothelial dysfunction, and affecting inflammatory cell activities in addition to amplifying and maintaining ADP-induced platelet activation and platelet aggregation. P2Y12 receptor inhibitors may also exert neuroprotective effects after ischemic stroke. Thus, P2Y12 receptor inhibitors may be a better choice for secondary prevention in patients with atherosclerotic ischemic stroke subtypes because of their triple functions (i.e., their anti-atherosclerotic, anti-platelet aggregation, and neuroprotective activities), and the P2Y12 receptor may also serve as a noval therapeutic target for atherosclerosis. In this review, we summarize the current knowledge on the P2Y12 receptor and its key roles in atherosclerosis and ischemic stroke of atherosclerotic origin.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (No. 81571139 to LM, No. 81571119 to BH) and National Key Research and Development Program of China (No. 2018YFC1312200).

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  1. Ying Gao and Cheng Yu contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Ying Gao, Shulan Pi, Ling Mao & Bo Hu

  2. Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Cheng Yu

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  1. Ying Gao
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Gao, Y., Yu, C., Pi, S. et al. The role of P2Y12 receptor in ischemic stroke of atherosclerotic origin. Cell. Mol. Life Sci. 76, 341–354 (2019). https://doi.org/10.1007/s00018-018-2937-2

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  • DOI: https://doi.org/10.1007/s00018-018-2937-2

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