Table of Contents
ISRN Vascular Medicine
Volume 2011 (2011), Article ID 165018, 6 pages
http://dx.doi.org/10.5402/2011/165018
Research Article

Resistance of Platelets in Hypercholesterolemia to Inhibition by Activated Coagulation Factor X

1Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA
2Department of Rehabilitation Medicine, New York, NY 10032, USA
3National Center of Excellence for the Medical Consequences of Spinal Cord Injury, USA
4Medical and Research Services, James J Peters Veterans Affairs Medical Center, Bronx, NY 10468, USA
5Jersey Shore University Medical Center 1945 Route 33 Neptune, NJ 07753, USA

Received 20 July 2011; Accepted 7 September 2011

Academic Editor: J. Komorowski

Copyright © 2011 Nighat Kahn et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Platelet hyperactivity may be involved in the pathogenesis of both thrombogenesis and hypercholesterolemia. The cholesterol-enriched states may contribute to accelerated development of atherosclerosis. The effect of high cholesterol on platelet activation and on inhibition by coagulation factor Xa, was studied in vitro. Incubation of normal platelets ( 𝑛 = 2 0 ) with cholesterol-rich dispersion resulted in a small increase of platelet aggregation (PA) and thromboxane A 2 ( T X A 2 ) synthesis when compared with platelets incubated with cholesterol-normal dispersion. In hypercholesterolemic patients ( 𝑛 = 2 0 ), ADP-induced PA and T X A 2 synthesis showed only small increases over normal controls. Addition of factor Xa (1 unit/mL) prevented the ADP-induced PA and markedly inhibited T X A 2 synthesis in normal platelets ( 1 . 3 Β± 0 . 2 and 8 . 7 Β± 2 . 0 pmol T X A 2 / 1 0 8 platelets, with and without factor Xa, resp.). However, factor Xa failed to significantly suppress T X A 2 synthesis in cholesterol-incubated normal platelets ( 9 . 5 Β± 1 . 4 and 1 1 . 8 Β± 1 . 3 pmol T X A 2 / 1 0 8 platelets, with and without factor Xa; resp., 𝑃 = N S ) as well as in platelets from patients with hypercholesterolemia ( 8 . 6 Β± 4 . 0 and 1 0 . 9 Β± 4 . 9 pmol T X A 2 / 1 0 8 platelets, with and without factor Xa; resp., 𝑃 = N S ). Exposure of platelets to high cholesterol concentrations, in vitro and in vivo, marginally increased PA and T X A 2 synthesis but resulted in loss of responsiveness to factor Xa, which could significantly contribute to platelet activation in hypercholesterolemic states.