Comparative antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist (XV454) and abciximab (c7E3) in flow models of thrombosis

James P. Abulencia, Niven Tien, Owen McCarty, Daniel Plymire, Shaker A. Mousa, Konstantinos Konstantopoulos

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Glycoprotein (GP) IIb/IIIa is pivotal in homotypic platelet aggregation and may also be involved in the heterotypic adhesion of leukocytes and tumor cells to platelets. This study was primarily undertaken to compare the antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist, XV454, to that of abciximab in 2 flow models of platelet thrombus formation: (1) direct shear-induced platelet aggregation imposed by a cone-and-plate rheometer and (2) platelet adhesion onto von Willebrand factor (vWF)/collagen I followed by aggregation in a perfusion system. XV454 inhibited platelet aggregation in a concentration-dependent manner in both experimental models. Maximal inhibition of aggregation was achieved by XV454 at ≈70% receptor occupancy, which is lower than the ≥85% previously reported for abciximab. At similar levels of receptor blockade (≈45%), XV454 appeared to be relatively more effective than abciximab in suppressing platelet aggregation. Neither XV454 nor abciximab inhibited platelet adhesion to collagen. Pretreatment of surface-adherent platelets with either XV454 or abciximab inhibited the attachment of monocytic THP-1 cells under flow. In contrast, the rapidly reversible GPIIb/IIIa inhibitor orbofiban failed to suppress these heterotypic interactions. These findings demonstrate that XV454 is a potent GPIIb/IIIa antagonist with a long receptor-bound lifetime like abciximab and may be beneficial for the treatment/prevention of thrombotic complications.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume21
Issue number1
StatePublished - 2001
Externally publishedYes

Fingerprint

Thrombosis
Platelet Aggregation
Blood Platelets
Collagen
Platelet Glycoprotein GPIIb-IIIa Complex
von Willebrand Factor
XV 454
abciximab
Leukocytes
Theoretical Models
Perfusion
Neoplasms

Keywords

  • Adhesion
  • Aggregation
  • Platelets
  • Shear stress
  • XV454, abciximab

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Comparative antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist (XV454) and abciximab (c7E3) in flow models of thrombosis. / Abulencia, James P.; Tien, Niven; McCarty, Owen; Plymire, Daniel; Mousa, Shaker A.; Konstantopoulos, Konstantinos.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 21, No. 1, 2001, p. 149-156.

Research output: Contribution to journalArticle

Abulencia, James P. ; Tien, Niven ; McCarty, Owen ; Plymire, Daniel ; Mousa, Shaker A. ; Konstantopoulos, Konstantinos. / Comparative antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist (XV454) and abciximab (c7E3) in flow models of thrombosis. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2001 ; Vol. 21, No. 1. pp. 149-156.
@article{ad4a4bb3611247e88c1360b4cf9ab278,
title = "Comparative antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist (XV454) and abciximab (c7E3) in flow models of thrombosis",
abstract = "Glycoprotein (GP) IIb/IIIa is pivotal in homotypic platelet aggregation and may also be involved in the heterotypic adhesion of leukocytes and tumor cells to platelets. This study was primarily undertaken to compare the antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist, XV454, to that of abciximab in 2 flow models of platelet thrombus formation: (1) direct shear-induced platelet aggregation imposed by a cone-and-plate rheometer and (2) platelet adhesion onto von Willebrand factor (vWF)/collagen I followed by aggregation in a perfusion system. XV454 inhibited platelet aggregation in a concentration-dependent manner in both experimental models. Maximal inhibition of aggregation was achieved by XV454 at ≈70{\%} receptor occupancy, which is lower than the ≥85{\%} previously reported for abciximab. At similar levels of receptor blockade (≈45{\%}), XV454 appeared to be relatively more effective than abciximab in suppressing platelet aggregation. Neither XV454 nor abciximab inhibited platelet adhesion to collagen. Pretreatment of surface-adherent platelets with either XV454 or abciximab inhibited the attachment of monocytic THP-1 cells under flow. In contrast, the rapidly reversible GPIIb/IIIa inhibitor orbofiban failed to suppress these heterotypic interactions. These findings demonstrate that XV454 is a potent GPIIb/IIIa antagonist with a long receptor-bound lifetime like abciximab and may be beneficial for the treatment/prevention of thrombotic complications.",
keywords = "Adhesion, Aggregation, Platelets, Shear stress, XV454, abciximab",
author = "Abulencia, {James P.} and Niven Tien and Owen McCarty and Daniel Plymire and Mousa, {Shaker A.} and Konstantinos Konstantopoulos",
year = "2001",
language = "English (US)",
volume = "21",
pages = "149--156",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Comparative antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist (XV454) and abciximab (c7E3) in flow models of thrombosis

AU - Abulencia, James P.

AU - Tien, Niven

AU - McCarty, Owen

AU - Plymire, Daniel

AU - Mousa, Shaker A.

AU - Konstantopoulos, Konstantinos

PY - 2001

Y1 - 2001

N2 - Glycoprotein (GP) IIb/IIIa is pivotal in homotypic platelet aggregation and may also be involved in the heterotypic adhesion of leukocytes and tumor cells to platelets. This study was primarily undertaken to compare the antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist, XV454, to that of abciximab in 2 flow models of platelet thrombus formation: (1) direct shear-induced platelet aggregation imposed by a cone-and-plate rheometer and (2) platelet adhesion onto von Willebrand factor (vWF)/collagen I followed by aggregation in a perfusion system. XV454 inhibited platelet aggregation in a concentration-dependent manner in both experimental models. Maximal inhibition of aggregation was achieved by XV454 at ≈70% receptor occupancy, which is lower than the ≥85% previously reported for abciximab. At similar levels of receptor blockade (≈45%), XV454 appeared to be relatively more effective than abciximab in suppressing platelet aggregation. Neither XV454 nor abciximab inhibited platelet adhesion to collagen. Pretreatment of surface-adherent platelets with either XV454 or abciximab inhibited the attachment of monocytic THP-1 cells under flow. In contrast, the rapidly reversible GPIIb/IIIa inhibitor orbofiban failed to suppress these heterotypic interactions. These findings demonstrate that XV454 is a potent GPIIb/IIIa antagonist with a long receptor-bound lifetime like abciximab and may be beneficial for the treatment/prevention of thrombotic complications.

AB - Glycoprotein (GP) IIb/IIIa is pivotal in homotypic platelet aggregation and may also be involved in the heterotypic adhesion of leukocytes and tumor cells to platelets. This study was primarily undertaken to compare the antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist, XV454, to that of abciximab in 2 flow models of platelet thrombus formation: (1) direct shear-induced platelet aggregation imposed by a cone-and-plate rheometer and (2) platelet adhesion onto von Willebrand factor (vWF)/collagen I followed by aggregation in a perfusion system. XV454 inhibited platelet aggregation in a concentration-dependent manner in both experimental models. Maximal inhibition of aggregation was achieved by XV454 at ≈70% receptor occupancy, which is lower than the ≥85% previously reported for abciximab. At similar levels of receptor blockade (≈45%), XV454 appeared to be relatively more effective than abciximab in suppressing platelet aggregation. Neither XV454 nor abciximab inhibited platelet adhesion to collagen. Pretreatment of surface-adherent platelets with either XV454 or abciximab inhibited the attachment of monocytic THP-1 cells under flow. In contrast, the rapidly reversible GPIIb/IIIa inhibitor orbofiban failed to suppress these heterotypic interactions. These findings demonstrate that XV454 is a potent GPIIb/IIIa antagonist with a long receptor-bound lifetime like abciximab and may be beneficial for the treatment/prevention of thrombotic complications.

KW - Adhesion

KW - Aggregation

KW - Platelets

KW - Shear stress

KW - XV454, abciximab

UR - http://www.scopus.com/inward/record.url?scp=0035154613&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035154613&partnerID=8YFLogxK

M3 - Article

VL - 21

SP - 149

EP - 156

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 1

ER -