The increased level of COX-dependent arachidonic acid metabolism in blood platelets from secondary progressive multiple sclerosis patients.

Agnieszka Morel,Elzbieta Miller,Michal Bijak,Joanna Saluk

doi:10.1007/s11010-016-2770-6

Abstract

Platelet activation is increasingly postulated as a possible component of the pathogenesis of multiple sclerosis (MS), especially due to the increased risk of cardiovascular events in MS. Arachidonic acid cascade metabolized by cyclooxygenase (COX) is a key pathway of platelet activation. The aim of our study was to investigate the COX-dependent arachidonic acid metabolic pathway in blood platelets from secondary progressive multiple sclerosis (SP MS) patients. The blood samples were obtained from 50 patients (man n = 22; female n = 28), suffering from SP MS, diagnosed according to the revised McDonald criteria. Platelet aggregation was measured in platelet-rich plasma after arachidonic acid stimulation. The level of COX activity and thromboxane B2 concentration were determined by ELISA method. Lipid peroxidation was assessed by measuring the level of malondialdehyde. The results were compared with a control group of healthy volunteers. We found that blood platelets obtained from SP MS patients were more sensitive to arachidonic acid and their response measured as platelet aggregation was stronger (about 14 %) relative to control. We also observed a significantly increased activity of COX (about 40 %) and synthesis of thromboxane B2 (about 113 %). The generation of malondialdehyde as a marker of lipid peroxidation was about 10 % higher in SP MS than in control. Cyclooxygenase-dependent arachidonic acid metabolism is significantly increased in blood platelets of patients with SP MS. Future clinical studies are required to recommend the use of low-dose aspirin, and possibly other COX inhibitors in the prevention of cardiovascular risk in MS.

Highlights

Multiple sclerosis (MS) is a chronic neuroinflammatory and immune-mediated disease associated with the formation of central nervous system (CNS) inflammatory plaques as well as lesions exhibiting extensive demyelination, along with loss of oligodendrocytes, neurons, and axons [1]
We found that blood platelets obtained from secondary progressive (SP) multiple sclerosis (MS) patients were more sensitive to arachidonic acid and their response measured as platelet aggregation was stronger relative to control
The level of platelet aggregation increased from 87 % for healthy control to 99 % for secondary progressive multiple sclerosis (SP MS) patients (Fig. 1a)

Summary

Introduction

Multiple sclerosis (MS) is a chronic neuroinflammatory and immune-mediated disease associated with the formation of central nervous system (CNS) inflammatory plaques as well as lesions exhibiting extensive demyelination, along with loss of oligodendrocytes, neurons, and axons [1]. There exists four subtypes of MS: relapsing-remitting (RR), secondary progressive (SP), primary progressive (PP), and progressive-relapsing (PR). The most prevalent form of MS is RR MS, in which the disease fluctuates between periods of inflammation and demyelination, and remission. After several years of disease duration, RR MS in approximately 70 % of cases, converts into a SP MS in which patients suffer irreversible disability progression. The progressive phase of MS is believed to be secondary to neurodegenerative changes triggered by inflammation. In progressive MS, as in relapsing-remitting MS, active tissue injury is associated

Objectives

Results

Conclusion