Table 1.

Reported involvement of platelet receptors and downstream signaling mediators in thrombus formation on inflamed or damaged endothelium

TargetInterventionFlow chamberShear rateEC sourceEC treatmentPlatelet sourceEffect intervention on thrombus formationReference
α5 CBL497 Ab Parallel plate 2.5 dynes/cm2 HUVECs Histamine WPs, fixed Platelet-VWF strings = 44 * 
α6 GoH3 Ab Parallel plate 150/s HUVECs Heat WB Platelet aggregate volume ↓ 40  
αvβ3 LM609 Ab Parallel plate 2.5 dynes/cm2 HUVECs Histamine WPs, fixed Platelet-VWF strings = , VWF strings = 44 * 
αIIbβ3/αvβ3 Abciximab (7E3, ReoPro) Parallel plate 1000/s HUVECs IFN-γ + TNF-α WPs Platelet SAC ↓ 59  
 Abciximab (7E3, ReoPro) Parallel plate 50 dynes/cm2 pPAECs Serum WB Platelet SAC ↓ 46  
 Abciximab (7E3, ReoPro) Parallel plate 750/s HUVECs, fixated TNF-α WB Platelet SAC ↓ 34  
 Abciximab (7E3, ReoPro) Capillary, rectangular 100/s pHUVECs TNF-α + TGF-β WPs + RBCs Platelet SAC ↓ 58  
 Abciximab (7E3, ReoPro) Bioflux 1000 5 dynes/cm2 PAECs Xenoactivation WB Platelet SAC, platelet aggregate volume ↓ 25  
 Abciximab (7E3, ReoPro) Parallel plate 150/s HUVECs Heat WB Platelet aggregate volume ↓ 40  
 β3 function neutralizing Ab Capillary, rectangular 140/s pHUVECs + pSMCs TGF-β1 WB Platelet SAC ↓ 47  
αIIbβ3 Eptifibatide (Integrilin) μ-slide VI 50/s LECs None WB Stable platelet-EC interactions = , platelet SAC ↑ 71  
 Eptifibatide (Integrilin) Branching microchannel 1-4, 10-40 dynes/cm2 HUVECs STX-2 WB Platelet aggregate volume ↓, channel occlusion ↓ 60  
 Eptifibatide (Integrilin) Branching microchannel 4 dynes/cm2 HUVECs FeCl3 WB Channel occlusion ↓ 26  
 Lotrafiban μ-slide VI 50/s LECs None WB, mouse Platelet SAC = 71  
 MA-16N7C2 Ab Parallel plate 24 dynes/cm2 Ea.hy926 PLPC WB, rec.† Platelet translocation = , number of adhered platelets ↓ 43  
 P2 mAb SPAA 170/s HUVECs None PRP, ADP stimulated Platelet SAC ↓ 57  
 P2 mAb Cone and plate, adapted 250/s pBAECs None PRP, TRAP-6 stimulated Number of adhered platelets ↓ 56  
 RGDS peptide Parallel plate 2.5 dynes/cm2 HUVECs Histamine WPs, fixed Platelet-VWF strings ↓, VWF strings ↓ 44 * 
 RGDS peptide SPAA 170/s HUVECs None PRP, ADP stimulated Platelet SAC ↓ 57  
 Ro 43-8857 SPAA 170/s HUVECs None PRP, ADP stimulated Platelet SAC ↓ 57  
 TAK-029 Not indicated 10/s HBECs None PRP, ADP stimulated Number of adhered platelets ↓ 85  
 TAK-029 Not indicated 10/s HAECs None PRP, ADP stimulated Number of adhered platelets ↓ 86  
ADAMTS13 ADAMTS13 function neutralizing pAb Capillary, rectangular 400/s pHUVECs TNF-α + TGF-β WPs + RBCs VWF strings ↑, platelets in VWF strings ↑ 58  
C5 Eculizumab Bioflux 200 3, 10 dynes/cm2 pPAECs Xenoactivation PRP Platelet SAC ↓ 23  
 Eculizumab Bioflux 200 3, 10 dynes/cm2 GTKO/hCD46-pPAECs Xenoactivation PRP Platelet SAC ↓ 23  
CD36 FA6.152 mAb Laboratory-Tek 1 100/s Ea.hy926 TNF-α WB, rec. Platelet SAC ↓ 65  
CD47 Agonist: 4N1k Laboratory-Tek 1 100/s Ea.hy926 TNF-α WB Platelet SAC ↑ 65  
 B6H12 mAb Parallel plate, Laboratory-Tek 1 100/s Ea.hy926 TNF-α WB Platelet SAC ↓ 65  
 Cd47−/− Parallel plate 100/s Ea.hy926 TNF-α WB, mouse Platelet SAC ↓ 65  
CLEC-2 Clec2−/− μ-slide VI 50/s LECs None WB, mouse Platelet SAC ↓ 71  
COX-1 Aspirin Branching microchannel 4 dynes/cm2 HUVECs FeCl3 WB Channel occlusion ↓ 26  
F-actin Cytochalasin D μ-slide VI 50/s LECs None WB Platelet SAC ↓ 71  
GPIbα 6D1 Ab Parallel plate 2.5 dynes/cm2 HUVECs Histamine WPs, fixed Platelet-VWF strings ↓, VWF strings = 44 * 
 AK2, SZ2 mAb’s Parallel plate 2 dynes/cm2 pHUVECs Histamine WPs + RBCs Platelet translocation ↓ 33  
 AK2 mAb Parallel plate 2.5 dynes/cm2 pHUVECs Histamine WPs Platelet-VWF strings ↓ 39  
 AK2 mAb Branching microchannel 10-30 dynes/cm2 HUVECs Shear WB, rec. Platelet adhesion ↓ 45  
 ATA Parallel plate 50 dynes/cm2 pPAECs Serum WB Platelet SAC ↓ 46  
 G19H10 Ab Parallel plate 24 dynes/cm2 Ea.hy926 PLPC WB, rec.† Platelet translocation ↓, number of adhered platelets ↓ 43  
 GPIbα function blocking Ab Parallel plate 150/s HUVECs Heat WB Platelet aggregate volume ↓ 40  
 GPIbα function neutralizing Ab Capillary, rectangular 140/s pHUVECs + pSMCs TGF-β1 WB Platelet SAC ↓ 47  
 GUR20-5 Ab Not indicated 10/s HBECs None PRP, ADP stimulated Number of adhered platelets = 85  
 GUR20-5 Ab Not indicated 10/s HAECs None PRP, ADP stimulated Number of adhered platelets = 86  
 IL4-R/Iba Branching microchannel 4 dynes/cm2 HUVECs FeCl3 WB, mouse Channel occlusion ↓ 26  
 SZ2 mAb Parallel plate 1000/s HUVECs IFN-γ + TNF-α WPs Platelet SAC ↓ 59  
 SZ2 mAb Capillary, rectangular 100/s pHUVECs TNF-α + TGF-β WPs + RBCs Platelet SAC ↓ 58  
PAR-1 Agonist: TRAP-6 Parallel plate 310/s Ea.hy926 None WB, rec. Number of adhered platelets ↑ 48  
 Agonist: TRAP-6 Parallel plate 24 dynes/cm2 Ea.hy926 PLPC WB, rec.† Platelet translocation ↓, number of adhered platelets ↑ 43  
P2X1 Agonist: ATP Rectangular Not indicated BPAECs None WPs Number of adhered platelets ↓ (ATP <50 nM), ↑ (ATP >100 nM) 64  
 Agonist: RBC derived ATP Rectangular Not indicated BPAECs None WPs + RBCs Number of adhered platelets ↓ 64  
 Glibenclamide Rectangular Not indicated BPAECs None WPs + RBCs Number of adhered platelets ↑ 64  
PDE/AR Theophylline Capillary, rectangular 140/s pHUVECs TGF-β1 WB Platelet SAC ↓ 47  
P-selectin Agonist: soluble P-selectin Parallel plate 2.5 dynes/cm2 HUVECs Histamine WPs, fixed Platelet-VWF strings ↓, VWF strings = 44 * 
 AK-6 mAb Cone and plate, adapted 250/s pBAECs None PRP, TRAP-6 stimulated Number of adhered platelets ↓ 56  
 CLB-Thromb/6 mAb Parallel plate 24 dynes/cm2 Ea.hy926 PLPC WB, rec.† Platelet translocation ↓, number of adhered platelets ↓ 43  
 pAb Parallel plate 2 dynes/cm2 pHUVECs Histamine WPs + RBCs Platelet translocation ↓ 33  
 pAb Parallel plate 2.5 dynes/cm2 HUVECs Histamine WPs, fixed Platelet-VWF strings = , VWF strings = 44 * 
 WASP12.2 Not indicated 6 dynes/cm2 HUVECs TNF-α WPs Number of adherent platelets ↓ 50  
Rac EHT1864 μ-slide VI 50/s LECs None WB Platelet SAC = 71  
SIRPα SE5A5 mAb Laboratory-Tek 1 100/s Ea.hy926 TNF-α WB, rec. Platelet SAC = 65  
Src Dasatinib μ-slide VI 50/s LECs None WB Stable platelet-EC interactions ↓, platelet SAC ↓ 71  
 Dasatinib μ-slide VI 50/s LECs None WB, mouse Platelet SAC ↓ 71  
Syk PRT060318 μ-slide VI 50/s LECs None WB Stable platelet-EC interactions ↓, platelet SAC = 71  
 Syk−/− μ-slide VI 50/s LECs None WB, mouse Platelet SAC ↓ 71  
Thrombin Bivalirudin Bioflux 1000 5 dynes/cm2 PAECs Xenoactivation WB Platelet SAC ↓, platelet aggregate volume ↓ 25  
 Hirudin, heparin Branching microchannel 4 dynes/cm2 HUVECs FeCl3 WB Channel occlusion ↓ 26  
 Ro 46-6240, hirudin, heparin Parallel plate 65/s pHUVECs TNF-α WB Number of platelet aggregates ↓ 24  
VCAM-1 1.4C3 Ab Capillary, rectangular 100/s pHUVECs TNF-α + TGF-β WPs + RBCs Platelet SAC = 58  
VWF 6G1 mAb Parallel plate 2.5 dynes/cm2 pHUVECs Histamine WPs Platelet-VWF strings ↓ 39  
 AJvW-2 Ab Parallel plate 24 dynes/cm2 Ea.hy926 PLPC WB, rec.† Platelet translocation ↓, number of adhered platelets ↓ 43  
 AJvW-2 Ab Not indicated 24 dynes/cm2 Aorta, rabbit Cholesterol diet WB, rec.† Platelet translocation ↓, number of adhered platelets ↓ 43  
 VWD type 3 Branching microchannel 4 dynes/cm2 HUVECs FeCl3 WB, rec. Channel occlusion ↓ 26  
TargetInterventionFlow chamberShear rateEC sourceEC treatmentPlatelet sourceEffect intervention on thrombus formationReference
α5 CBL497 Ab Parallel plate 2.5 dynes/cm2 HUVECs Histamine WPs, fixed Platelet-VWF strings = 44 * 
α6 GoH3 Ab Parallel plate 150/s HUVECs Heat WB Platelet aggregate volume ↓ 40  
αvβ3 LM609 Ab Parallel plate 2.5 dynes/cm2 HUVECs Histamine WPs, fixed Platelet-VWF strings = , VWF strings = 44 * 
αIIbβ3/αvβ3 Abciximab (7E3, ReoPro) Parallel plate 1000/s HUVECs IFN-γ + TNF-α WPs Platelet SAC ↓ 59  
 Abciximab (7E3, ReoPro) Parallel plate 50 dynes/cm2 pPAECs Serum WB Platelet SAC ↓ 46  
 Abciximab (7E3, ReoPro) Parallel plate 750/s HUVECs, fixated TNF-α WB Platelet SAC ↓ 34  
 Abciximab (7E3, ReoPro) Capillary, rectangular 100/s pHUVECs TNF-α + TGF-β WPs + RBCs Platelet SAC ↓ 58  
 Abciximab (7E3, ReoPro) Bioflux 1000 5 dynes/cm2 PAECs Xenoactivation WB Platelet SAC, platelet aggregate volume ↓ 25  
 Abciximab (7E3, ReoPro) Parallel plate 150/s HUVECs Heat WB Platelet aggregate volume ↓ 40  
 β3 function neutralizing Ab Capillary, rectangular 140/s pHUVECs + pSMCs TGF-β1 WB Platelet SAC ↓ 47  
αIIbβ3 Eptifibatide (Integrilin) μ-slide VI 50/s LECs None WB Stable platelet-EC interactions = , platelet SAC ↑ 71  
 Eptifibatide (Integrilin) Branching microchannel 1-4, 10-40 dynes/cm2 HUVECs STX-2 WB Platelet aggregate volume ↓, channel occlusion ↓ 60  
 Eptifibatide (Integrilin) Branching microchannel 4 dynes/cm2 HUVECs FeCl3 WB Channel occlusion ↓ 26  
 Lotrafiban μ-slide VI 50/s LECs None WB, mouse Platelet SAC = 71  
 MA-16N7C2 Ab Parallel plate 24 dynes/cm2 Ea.hy926 PLPC WB, rec.† Platelet translocation = , number of adhered platelets ↓ 43  
 P2 mAb SPAA 170/s HUVECs None PRP, ADP stimulated Platelet SAC ↓ 57  
 P2 mAb Cone and plate, adapted 250/s pBAECs None PRP, TRAP-6 stimulated Number of adhered platelets ↓ 56  
 RGDS peptide Parallel plate 2.5 dynes/cm2 HUVECs Histamine WPs, fixed Platelet-VWF strings ↓, VWF strings ↓ 44 * 
 RGDS peptide SPAA 170/s HUVECs None PRP, ADP stimulated Platelet SAC ↓ 57  
 Ro 43-8857 SPAA 170/s HUVECs None PRP, ADP stimulated Platelet SAC ↓ 57  
 TAK-029 Not indicated 10/s HBECs None PRP, ADP stimulated Number of adhered platelets ↓ 85  
 TAK-029 Not indicated 10/s HAECs None PRP, ADP stimulated Number of adhered platelets ↓ 86  
ADAMTS13 ADAMTS13 function neutralizing pAb Capillary, rectangular 400/s pHUVECs TNF-α + TGF-β WPs + RBCs VWF strings ↑, platelets in VWF strings ↑ 58  
C5 Eculizumab Bioflux 200 3, 10 dynes/cm2 pPAECs Xenoactivation PRP Platelet SAC ↓ 23  
 Eculizumab Bioflux 200 3, 10 dynes/cm2 GTKO/hCD46-pPAECs Xenoactivation PRP Platelet SAC ↓ 23  
CD36 FA6.152 mAb Laboratory-Tek 1 100/s Ea.hy926 TNF-α WB, rec. Platelet SAC ↓ 65  
CD47 Agonist: 4N1k Laboratory-Tek 1 100/s Ea.hy926 TNF-α WB Platelet SAC ↑ 65  
 B6H12 mAb Parallel plate, Laboratory-Tek 1 100/s Ea.hy926 TNF-α WB Platelet SAC ↓ 65  
 Cd47−/− Parallel plate 100/s Ea.hy926 TNF-α WB, mouse Platelet SAC ↓ 65  
CLEC-2 Clec2−/− μ-slide VI 50/s LECs None WB, mouse Platelet SAC ↓ 71  
COX-1 Aspirin Branching microchannel 4 dynes/cm2 HUVECs FeCl3 WB Channel occlusion ↓ 26  
F-actin Cytochalasin D μ-slide VI 50/s LECs None WB Platelet SAC ↓ 71  
GPIbα 6D1 Ab Parallel plate 2.5 dynes/cm2 HUVECs Histamine WPs, fixed Platelet-VWF strings ↓, VWF strings = 44 * 
 AK2, SZ2 mAb’s Parallel plate 2 dynes/cm2 pHUVECs Histamine WPs + RBCs Platelet translocation ↓ 33  
 AK2 mAb Parallel plate 2.5 dynes/cm2 pHUVECs Histamine WPs Platelet-VWF strings ↓ 39  
 AK2 mAb Branching microchannel 10-30 dynes/cm2 HUVECs Shear WB, rec. Platelet adhesion ↓ 45  
 ATA Parallel plate 50 dynes/cm2 pPAECs Serum WB Platelet SAC ↓ 46  
 G19H10 Ab Parallel plate 24 dynes/cm2 Ea.hy926 PLPC WB, rec.† Platelet translocation ↓, number of adhered platelets ↓ 43  
 GPIbα function blocking Ab Parallel plate 150/s HUVECs Heat WB Platelet aggregate volume ↓ 40  
 GPIbα function neutralizing Ab Capillary, rectangular 140/s pHUVECs + pSMCs TGF-β1 WB Platelet SAC ↓ 47  
 GUR20-5 Ab Not indicated 10/s HBECs None PRP, ADP stimulated Number of adhered platelets = 85  
 GUR20-5 Ab Not indicated 10/s HAECs None PRP, ADP stimulated Number of adhered platelets = 86  
 IL4-R/Iba Branching microchannel 4 dynes/cm2 HUVECs FeCl3 WB, mouse Channel occlusion ↓ 26  
 SZ2 mAb Parallel plate 1000/s HUVECs IFN-γ + TNF-α WPs Platelet SAC ↓ 59  
 SZ2 mAb Capillary, rectangular 100/s pHUVECs TNF-α + TGF-β WPs + RBCs Platelet SAC ↓ 58  
PAR-1 Agonist: TRAP-6 Parallel plate 310/s Ea.hy926 None WB, rec. Number of adhered platelets ↑ 48  
 Agonist: TRAP-6 Parallel plate 24 dynes/cm2 Ea.hy926 PLPC WB, rec.† Platelet translocation ↓, number of adhered platelets ↑ 43  
P2X1 Agonist: ATP Rectangular Not indicated BPAECs None WPs Number of adhered platelets ↓ (ATP <50 nM), ↑ (ATP >100 nM) 64  
 Agonist: RBC derived ATP Rectangular Not indicated BPAECs None WPs + RBCs Number of adhered platelets ↓ 64  
 Glibenclamide Rectangular Not indicated BPAECs None WPs + RBCs Number of adhered platelets ↑ 64  
PDE/AR Theophylline Capillary, rectangular 140/s pHUVECs TGF-β1 WB Platelet SAC ↓ 47  
P-selectin Agonist: soluble P-selectin Parallel plate 2.5 dynes/cm2 HUVECs Histamine WPs, fixed Platelet-VWF strings ↓, VWF strings = 44 * 
 AK-6 mAb Cone and plate, adapted 250/s pBAECs None PRP, TRAP-6 stimulated Number of adhered platelets ↓ 56  
 CLB-Thromb/6 mAb Parallel plate 24 dynes/cm2 Ea.hy926 PLPC WB, rec.† Platelet translocation ↓, number of adhered platelets ↓ 43  
 pAb Parallel plate 2 dynes/cm2 pHUVECs Histamine WPs + RBCs Platelet translocation ↓ 33  
 pAb Parallel plate 2.5 dynes/cm2 HUVECs Histamine WPs, fixed Platelet-VWF strings = , VWF strings = 44 * 
 WASP12.2 Not indicated 6 dynes/cm2 HUVECs TNF-α WPs Number of adherent platelets ↓ 50  
Rac EHT1864 μ-slide VI 50/s LECs None WB Platelet SAC = 71  
SIRPα SE5A5 mAb Laboratory-Tek 1 100/s Ea.hy926 TNF-α WB, rec. Platelet SAC = 65  
Src Dasatinib μ-slide VI 50/s LECs None WB Stable platelet-EC interactions ↓, platelet SAC ↓ 71  
 Dasatinib μ-slide VI 50/s LECs None WB, mouse Platelet SAC ↓ 71  
Syk PRT060318 μ-slide VI 50/s LECs None WB Stable platelet-EC interactions ↓, platelet SAC = 71  
 Syk−/− μ-slide VI 50/s LECs None WB, mouse Platelet SAC ↓ 71  
Thrombin Bivalirudin Bioflux 1000 5 dynes/cm2 PAECs Xenoactivation WB Platelet SAC ↓, platelet aggregate volume ↓ 25  
 Hirudin, heparin Branching microchannel 4 dynes/cm2 HUVECs FeCl3 WB Channel occlusion ↓ 26  
 Ro 46-6240, hirudin, heparin Parallel plate 65/s pHUVECs TNF-α WB Number of platelet aggregates ↓ 24  
VCAM-1 1.4C3 Ab Capillary, rectangular 100/s pHUVECs TNF-α + TGF-β WPs + RBCs Platelet SAC = 58  
VWF 6G1 mAb Parallel plate 2.5 dynes/cm2 pHUVECs Histamine WPs Platelet-VWF strings ↓ 39  
 AJvW-2 Ab Parallel plate 24 dynes/cm2 Ea.hy926 PLPC WB, rec.† Platelet translocation ↓, number of adhered platelets ↓ 43  
 AJvW-2 Ab Not indicated 24 dynes/cm2 Aorta, rabbit Cholesterol diet WB, rec.† Platelet translocation ↓, number of adhered platelets ↓ 43  
 VWD type 3 Branching microchannel 4 dynes/cm2 HUVECs FeCl3 WB, rec. Channel occlusion ↓ 26  

All platelet sources are of human origin unless indicated otherwise. Decreased (↓); no change (=); increased (↑).

Ab, antibody; ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; AR, adenosine receptor; ATA, aurin tricarboxylic acid; ATP, adenosine triphosphate; BPAEC, bovine pulmonary artery endothelial cell; C5, complement component; CLEC-2, c-type lectinlike receptor 2; COX-1, cyclooxygenase 1; GTKO/hCD46-pPAEC, alpha1.3-galactosyltransferase deficient/human CD46 transgenic-primary porcine aortic endothelial cell; HAEC, human aortic endothelial cell; HBEC, human brain microvascular endothelial cell; HUVEC, human umbilical vein endothelial cell; IL, interleukin; INF-γ, interferon-γ; LEC, lymphatic endothelial cell; mAb, monoclonal antibody; pAb, polyclonal antibody; PAEC, porcine aortic endothelial cell; pBAEC, primary bovine aortic endothelial cell; pHUVEC, primary human umbilical vein endothelial cell; PLPC, palmitoyllysophosphatidylcholine; PLCγ2, phosholipase γ2; PMA, phorbol-12-myristate-13-acetate; pPAEC, primary porcine aortic endothelial cell; PRP, platelet-rich plasma; pSMC, primary smooth muscle cell; rec., reconstituted; RGDS, arginine glycine asparagine serine; SAC, surface area coverage; SIRPα, signal regulatory protein α; SPAA, stagnation point flow adhesio-aggregometer; STX-2, shiga toxin 2; TGF-β1, transforming growth factor β1; TNF-α, tumor necrosis factor α; TRAP-6, thrombin receptor-activating peptide 6; VCAM-1, vascular cell adhesion molecule 1; VWD, von Willebrand disease; WB, whole blood; WP, washed platelet.

*

No statistics applied.

†

Spiked with TRAP-6-activated platelets.

View Large
Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal