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The Role and Molecular Mechanism of P2Y12 Receptors in the Pathogenesis of Atherosclerotic Cardiovascular Diseases

Journal

APPLIED SCIENCES-BASEL
Volume 11, Issue 19, Pages -

Publisher

MDPI
DOI: 10.3390/app11199078

Keywords

P2Y12 receptor; cardiovascular disease; fluid shear stress

Funding

  1. National Natural Science Foundation of China [31971242]
  2. Chongqing Science and Technology Bureau [cstc2019jcyj-zdxmX0028]
  3. State Key Project Specialized for Infectious Diseases [2017ZX10201201-001-005, 2017ZX10201201-002-005]
  4. Chongqing Municipal Education Commission, China [KYYJ202001]

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The P2Y receptor family, primarily activated by ATP, ADP, UTP, and UDP, plays a crucial role in platelet aggregation, vascular remodeling, and atherosclerosis. Inhibition of P2Y12 receptor-induced diseases with inhibitors like ticagrelor and clopidogrel still faces challenges, such as limited antithrombotic effects.
The P2Y receptor family is a class of G protein-coupled receptors activated primarily by adenosine triphosphate (ATP), adenosine diphosphate (ADP), uridine triphosphate (UTP) and uridine diphosphate (UDP). The P2Y12 receptor is expressed on platelets which mediates platelet aggregation and morphological changes. At the same time, during the process of vascular remodeling and atherosclerosis, ADP can also promote the migration and proliferation of vascular smooth muscle and endothelial cells through P2Y12 receptor activating. Furthermore, P2Y12 is involved in many signal transductions processes, such as intimal hyperplasia, monocyte infiltration and so on, which play an important role in immune inflammation and brain injury. In order to solve the diseases induced by P2Y12 receptor, inhibitors such as ticagrelor, clopidogrel were widely used for cardiovascular diseases. However, there were some problems, such as limited antithrombotic effect, remain unsolved. This article summarizes the role and molecular mechanism of P2Y12 receptors in the pathogenesis of cardiovascular-related diseases, providing in-depth expounding on the molecular mechanism of P2Y12 receptor inhibitors and contributing to the treatment of diseases based on P2Y12 receptors.

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