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

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.

Increased level of fibrinogen chains in the proteome of blood platelets in secondary progressive multiple sclerosis patients

“…After several years of the disease's duration, when the axons have lost their ability to regenerate, in more than 80% of cases RRMS turns into a secondary progressive stage (SPMS), in which the patient suffers irreversible progressive disability. [12][13][14] The available data, including our previous studies, clearly indicate excessive intravascular activation of these cells and their hyperresponsiveness to the number of physiological activators in SPMS. 3 The nature of the pathophysiology of MS is very complex and almost always involves multiple types of cells.…”

“…That is, ischaemic events are directly associated with irregular platelet functions and their prothrombotic activity. [12][13][14] A study scheduled by our research group will, for the first time, direct the search for the origins of the hyperactivity of platelets towards molecular changes within platelets in SPMS. 17 Our existing findings state that platelet activation is an epiphenomenon consequent to the progression of MS, and probably secondary to endothelial injury, which causes the exposure of platelets to a variety of stimuli.…”

The physiology of blood platelets and changes of their biological activities in multiple sclerosis

“…The possible involvement of platelets in MS was first investigated by Putnam in 1937(Putnam 1937). In the 1950-1960s several studies (Nathanson andSavitsky 1952, Wright et al 1965) were focused on the relations of platelets to CNS demyelination and reported increased platelet adhesiveness correlated with activity of MS (Morel et al 2015(Morel et al , 2016) (such as fibrin, tissue factor, protein C) in lesion of MS patients suggests procoagulant state (Han et al 2008). Abnormalities of platelet reactivity in MS patients and chronic platelet activation in MS seem to be well established (Morel et al 2015(Morel et al , 2016.…”

“…In the 1950-1960s several studies (Nathanson andSavitsky 1952, Wright et al 1965) were focused on the relations of platelets to CNS demyelination and reported increased platelet adhesiveness correlated with activity of MS (Morel et al 2015(Morel et al , 2016) (such as fibrin, tissue factor, protein C) in lesion of MS patients suggests procoagulant state (Han et al 2008). Abnormalities of platelet reactivity in MS patients and chronic platelet activation in MS seem to be well established (Morel et al 2015(Morel et al , 2016. Sheremata and others (2008) reported increased platelet activation assessed by the elevated levels of platelet activation markers such as platelet MPs and P-selectin on platelet membranes in MS patients.…”

Pathogenesis and Progression of Multiple Sclerosis: The Role of Arachidonic Acid–Mediated Neuroinflammation

“…The combination of COX-2 and 5-LOX selective inhibitors has the potential to improve multiple sclerosis pathology. Moreover, multiple sclerosis has been associated with platelet activation and augmented cardiovascular risk, which are considered as causal factors in the pathogenesis of the disease (57,58). Interestingly, it has been recently observed that peripheral blood platelets of patients highly express COX-2 (58).…”