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

Abstract

Epidemiological studies indicate a high risk of stroke, heart failure and myocardial infarction in patients with multiple sclerosis, especially in its secondary progressive (SPMS) phase. Some ischaemic events are directly associated with abnormal platelet functions and their prothrombotic activity. Recent reports, including this study, confirm the increased activation of circulating platelets in SPMS, and also show increased platelet reactivity, among other responses, as well as strong aggregation. In this current study, we conducted a comparative analysis of the platelet proteome in SPMS patients and in healthy controls, to demonstrate the quantitative and qualitative differences likely to affect functional changes observed in SPMS. During densitometry evaluation of 2‐D fluorescence difference gel electrophoresis, we observed differences between the electrophoretic patterns of SPMS platelets and the control samples. To determine a detailed characterisation of the proteome changes in the SPMS patients’ blood platelets, in the next stage, we performed mass spectrometry of selected spots and indicated the increased presence of four proteins (fibrinogen, α‐2 macroglobulin, septin‐14 and tubulin β‐1 chain). The most important of these is the increased amount of prothrombotic protein, fibrinogen, which seems to confirm the accuracy of the imaging and potentially explains the increased risk of platelet‐origin thrombotic events. This study provides new knowledge of the potential existence of the molecular mechanisms responsible for the acceleration of the platelet pro‐coagulant function in SPMS. This can help to identify new targets for therapy, which can then be used not only in the second stage of the disease.

Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis

“…In our previous work, analyzing proteome of platelets using a 2-dimensional electrophoresis (2-DE) method together with mass spectrometry (MALDI/TOF-TOF) analysis, we reported a higher level of α2M in SP MS patients compared to control group [ 18 ]. It is mainly produced by the liver, but also locally synthesized by blood cells.…”

“…The chronic activation of blood platelets in SP MS, as expressed by high levels of activation markers, altered mitochondrial function, and increased platelet reactivity, has been proven in our previous studies to focus exclusively on the progressive stage of MS, characterized with an especially high risk of CVD [ 15 , 16 , 17 ]. Furthermore, our findings have demonstrated changes in the protein profile, manifesting an enhanced level of blood coagulation factors [ 18 ].…”

Metformin as a Potential Agent in the Treatment of Multiple Sclerosis

“…Fibrin clot formation, leading to vessel occlusion, represents the terminal step in the atherothrombotic process and involves a variety of interactions between coagulation factors and blood platelets [ 132 ]. Many studies, including our research, indicate an increased number of platelet-derived microparticles and enhanced P-selection expression, which are accepted markers of platelet activation in EAE/MS [ 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 ]. Disruption of the BBB permeability causes a massive infiltration of many leukocytes that elicit neurotrophic changes, leading to demyelination in the CNS [ 142 ].…”

Oxidative Damage of Blood Platelets Correlates with the Degree of Psychophysical Disability in Secondary Progressive Multiple Sclerosis

“…However, available clinical data have confirmed the elevated activation of circulating platelets in MS [48]. Our previous study revealed an increase in the prothrombotic and proinflammatory properties of platelets [11,49,50]. In neurobiological studies, blood platelets are regarded as a cellular model for the analysis of metabolic pathways related to the pathogenesis of MS and the regulation of oxidative stress [49,51].…”