title: Role of P2Y12Receptor in Thrombosis.
abstract: P2Y12receptor is a 342 amino acid Gi-coupled receptor predominantly expressed on platelets. P2Y12receptor is physiologically activated by ADP and inhibits adenyl cyclase (AC) to decrease cyclic AMP (cAMP) level, resulting in platelet aggregation. It also activates PI3 kinase (PI3K) pathway leading to fibrinogen receptor activation, and may protect platelets from apoptosis. Abnormalities of P2Y12receptor include congenital deficiencies or high activity in diseases like diabetes mellitus (DM) and chronic kidney disease (CKD), exposing such patients to a prothrombotic condition. A series of clinical antiplatelet drugs, such as clopidogrel and ticagrelor, are designed as indirect or direct antagonists of P2Y12receptor to reduce incidence of thrombosis mainly for patients of acute coronary syndrome (ACS) who are at high risk of thrombotic events. Studies on novel dual-/multi-target antiplatelet agents consider P2Y12receptor as a promising part in combined targets. However, the clinical practical phenomena, such as "clopidogrel resistance" due to gene variations of cytochrome P450 or P2Y12receptor constitutive activation, call for better antiplatelet agents. Researches also showed inverse agonist of P2Y12receptor could play a better role over neutral antagonists. Personalized antiplatelet therapy is the most ideal destination for antiplatelet therapy in ACS patients with or without other underlying diseases like DM or CKD, however, there is still a long way to go.
authors.affiliation: Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China. dingzr@fudan.edu.cn.
authors.forename: Zhongren
authors.initials: Z
authors.lastname: Ding
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D000241:Adenosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000244:Adenosine Diphosphate / Q000097:blood*; D000262:Adenylyl Cyclases / Q000097:blood* / Q000235:genetics; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000077144:Clopidogrel; D000242:Cyclic AMP / Q000097:blood*; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000097:blood / Q000235:genetics; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D039341:Receptors, Fibrinogen / Q000097:blood / Q000235:genetics; D058925:Receptors, Purinergic P2Y12 / Q000097:blood* / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D013927:Thrombosis / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D039341:Receptors, Fibrinogen; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D000262:Adenylyl Cyclases; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Abnormalities; Antagonists; P2Y12 receptor; Platelet; Signal transductions