The role of P2Y12 receptor inhibition in ischemic stroke on microglia, platelets and vascular smooth muscle cells
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The role of P2Y12 receptor inhibition in ischemic stroke on microglia, platelets and vascular smooth muscle cells Fengyang Li1 · Dan Xu1 · Kai Hou1 · Xue Gou1 · Yunman Li1
© Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Ischemic stroke · P2Y12 receptors · Microglia · Platelets · VSMCs
Highlights • Apart from platelet, P2Y12 receptor is also expressed on
microglia, VSMCs and immune cells.
• P2Y12 activation participates in the whole pathogenesis
of ischemic stroke.
• High expression of P2Y12 receptors on microglia appears
limitedly in the early stage of post-stroke.
• Activated platelet releases numerous inflammatory fac-
tors and mediates inflammatory cell infiltration.
* Yunman Li [email protected] Fengyang Li [email protected] Dan Xu [email protected] Kai Hou [email protected] Xue Gou [email protected] 1
State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, People’s Republic of China
Introduction Cerebral ischemia is the third major cause of death and the commonest cause of permanent disability, becoming a huge economic and social burden for the elderly around the world. Clinically, stroke is classified into two types, ischemic stroke and hemorrhagic stroke with ischemic stroke accounting for about 85% [1]. There are many pathologies associated with ischemic stroke, including atherosclerosis, cardiogenic embolism, and small vessel occlusion. Large artery atherosclerosis is the primary cause of stroke, relating to the formation of plateletrich emboli in cerebral vessel occlusion [2, 3]. The earliest changes in the sites of atherosclerotic lesions are associated with infiltration of lipid and macrophage and subsequent endothelial cells (EC) dysfunction. After intimal injury, EC, platelet and inflammatory cells release cytokines and growth factors that trigger vascular smooth muscle cells (VSM
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