Platelet Signaling Pathways and New Inhibitors

被引:43
作者
Grover, Steven P. [1 ]
Bergmeier, Wolfgang [2 ,3 ]
Mackman, Nigel [1 ]
机构
[1] Univ North Carolina Chapel Hill, Dept Med, Div Hematol & Oncol, Thrombosis & Hemostasis Program, Chapel Hill, NC USA
[2] Univ North Carolina Chapel Hill, McAllister Heart Inst, Chapel Hill, NC USA
[3] Univ North Carolina Chapel Hill, Dept Biochem & Biophys, Chapel Hill, NC USA
关键词
hemostasis; myocardial infarction; platelet activation; stroke; thrombosis; CLASS-III PI3K; ARTERIAL THROMBOSIS; PHOSPHATIDYLSERINE EXPOSURE; GLYCOPROTEIN VI; PROTECTS MICE; NADPH-OXIDASE; TRPM7; CHANNEL; EX-VIVO; RECEPTOR; ACTIVATION;
D O I
10.1161/ATVBAHA.118.310224
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Recent studies have revealed a series of novel mechanisms that either positively or negatively regulate signaling events downstream of receptor-mediated platelet activation. In several cases, it seems that disruption of these pathways can selectively inhibit thrombosis while leaving essential hemostatic processes largely intact. These pathways may be of considerable interest as potential targets for development of a new generation of antiplatelet agents. Other work has focused on the development of novel antiplatelet agents that inhibit established targets such as P2Y12, PAR1, and GPVI. These agents may overcome some of the limitations of established therapies. It remains to be determined if these novel agents will find clinical use. © 2018 American Heart Association, Inc.
引用
收藏
页码:e28 / e35
页数:8
相关论文
共 93 条
  • [31] Cell-Penetrating Pepducin Therapy Targeting PAR1 in Subjects With Coronary Artery Disease
    Gurbel, Paul A.
    Bliden, Kevin P.
    Turner, Susan E.
    Tantry, Udaya S.
    Gesheff, Martin G.
    Barr, Travis P.
    Covic, Lidija
    Kuliopulos, Athan
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2016, 36 (01) : 189 - 197
  • [32] PAR4 (Protease-Activated Receptor 4) PARticularly Important 4 Antiplatelet Therapy
    Han, Xu
    Nieman, Marvin T.
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2018, 38 (02) : 287 - 289
  • [33] Charming the Snake Venom-Derived Peptides Show Surprising Efficacy as Glycoprotein VI-Targeting Antithrombotic Agents
    Herr, Andrew B.
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2017, 37 (07) : 1266 - 1268
  • [34] Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E
    Huo, YQ
    Schober, A
    Forlow, SB
    Smith, DF
    Hyman, MC
    Jung, S
    Littman, DR
    Weber, C
    Ley, K
    [J]. NATURE MEDICINE, 2003, 9 (01) : 61 - 67
  • [35] Glutathione Peroxidase-3 Deficiency Promotes Platelet-Dependent Thrombosis In Vivo
    Jin, Richard C.
    Mahoney, Christopher E.
    Anderson, Laura
    Ottaviano, Filomena
    Croce, Kevin
    Leopold, Jane A.
    Zhang, Ying-Yi
    Tang, Shiow-Shih
    Handy, Diane E.
    Loscalzo, Joseph
    [J]. CIRCULATION, 2011, 123 (18) : 1963 - 1973
  • [36] Critical role for the mitochondrial permeability transition pore and cyclophilin D in platelet activation and thrombosis
    Jobe, Shawn M.
    Wilson, Katina M.
    Leo, Lorie
    Raimondi, Alejandro
    Molkentin, Jeffery D.
    Lentz, Steven R.
    Di Paola, Jorge
    [J]. BLOOD, 2008, 111 (03) : 1257 - 1265
  • [37] Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin
    Kahn, ML
    Nakanishi-Matsui, M
    Shapiro, MJ
    Ishihara, H
    Coughlin, SR
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (06) : 879 - 887
  • [38] Membrane potential-dependent inhibition of platelet adhesion to endothelial cells by epoxyeicosatrienoic acids
    Krötz, F
    Riexinger, T
    Buerkle, MA
    Nithipatikom, K
    Gloe, T
    Sohn, HY
    Campbell, WB
    Pohl, U
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2004, 24 (03) : 595 - 600
  • [39] Genetic and pharmacological analyses of Syk function in αIIbβ3 signaling in platelets
    Law, DA
    Nannizzi-Alaimo, L
    Ministri, K
    Hughes, PE
    Forsyth, J
    Turner, M
    Shattil, SJ
    Ginsberg, MH
    Tybulewicz, VLJ
    Phillips, DR
    [J]. BLOOD, 1999, 93 (08) : 2645 - 2652
  • [40] Collagens are functional, high affinity ligands for the inhibitory immune receptor LAIR-1
    Lebbink, Robert Jan
    de Ruiter, Talitha
    Adelmeijer, Jelle
    Brenkman, Arjan B.
    van Helvoort, Joop M.
    Koch, Manuel
    Farndale, Richard W.
    Lisman, Ton
    Sonnenberg, Arnoud
    Lenting, Peter J.
    Meyaard, Linde
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (06) : 1419 - 1425