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The role of P2Y12 receptor inhibition in ischemic stroke on microglia, platelets and vascular smooth muscle cells

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Abstract

P2Y12 receptors on platelets have long been the main target of antiplatelet drugs. However, a growing number of studies have revealed that P2Y12 receptor activation on microglia and vascular smooth muscle cells (VSMCs) also aggravates ischemic stroke injury. The proliferation and migration of VSMCs in the vascular wall have important influence on the early lesion of atherosclerosis, which may lead to the origin of cerebral ischemic attack of atherosclerosis. Blockage of cellular P2Y12 receptors could inhibit microglial activation, block formation of platelet-leukocyte aggregates, reduce proinflammatory cytokine levels and suppress migration and proliferation of VSMCs, implying that apart from anti-thrombotic effect, P2Y12 inhibitors have additional neuroprotective, anti-inflammatory and anti-atherosclerotic therapeutic benefits against ischemic stroke. In this review, we will summarize recent advances in studies on P2Y12 receptors and emphatically introduce their significance in microglia, platelets and VSMCs after ischemic stroke, discussing how to exert the beneficial effects of P2Y12 inhibition.

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Acknowledgments

This project was supported by National Science and Technology Major Project of the Ministry of Science and Technology of China (Grant No. 2016ZX09101031) and (Grant No. 2018ZX09301043) and China Pharmaceutical University “Double First-Class” Construction Technology Innovation Team Project (Grant No. CPU2018GY23) and (Grant No. CPU2018GY24).

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  1. State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Fengyang Li, Dan Xu, Kai Hou, Xue Gou & Yunman Li

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FL and DX were involved in collecting information and writing a draft manuscript; KH and XG performed information consolidation and were involved in modifying article; YL was involved in selecting theme. All authors read and approved the final manuscript.

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Li, F., Xu, D., Hou, K. et al. The role of P2Y12 receptor inhibition in ischemic stroke on microglia, platelets and vascular smooth muscle cells. J Thromb Thrombolysis 50, 874–885 (2020). https://doi.org/10.1007/s11239-020-02098-4

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