Platelet-Derived Drug Targets and Biomarkers of Ischemic Stroke-The First Dynamic Human LC-MS Proteomic Study.

Karolina Gawryś,Janusz Dębski,Maciej Jakubowski,Arkadiusz Derkacz,Jakub Gawryś,Adrian Doroszko,Małgorzata Trocha,Aleksandra Turek-Jakubowska,Ewa Szahidewicz-Krupska

doi:10.3390/jcm11051198

Abstract

(1) Objective: The aim of this dynamic LC-MS (liquid chromatography and mass spectrometry) human platelet proteomic study was to identify the potential proteins candidates for biomarkers of acute ischemic stroke (AIS), their changes during the acute phase of stroke and to define potential novel drug targets. (2) Methods: A total of 32 patients (18–80 years old) were investigated that presented symptoms of AIS lasting less than 24 h from the onset, confirmed by neurological examination and/or new cerebral ischemia visualized in the CT (computed-tomography) scans. The analysis of platelet proteome was performed using LC-MS at baseline, and then on the third and seventh day from the onset of symptoms. The control group was demographically matched without any clinical signs of acute brain injury. (3) Results: The differences between platelets, at 24 h after first symptoms of stroke subjects and the control group included: β-amyloid A4 and amyloid-like protein 2, coactosin-like protein, thymidine phosphorylase 4 (TYMP-4), interferon regulatory factor 7 (IRF7), vitamin K-dependent protein S, histone proteins (H2A type 1 and 1-A, H2A types 2B and J, H2Av, -z, and -x), and platelet basic protein. The dynamic changes in the platelet protein concentration involved thrombospondin-1, thrombospondin-2, filamin A, B, and C. (4) Conclusions: This is the first human dynamic LC-MS proteomic study that differentiates platelet proteome in the acute phase of ischemic stroke in time series and compares the results with healthy controls. Identified proteins may be considered as future markers of ischemic stroke or therapeutic drug targets. Thymidine phosphorylase 4 (TYMP-4) holds promise as an interesting drug target in the management or prevention of ischemic stroke.

Highlights

Cardiovascular disease (CVD) remains among the most common causes of morbidity and mortality, as reported worldwide annually
In the complete blood count (CBC), significantly lower mean platelet volume (MPV) and significantly higher mean corpuscular hemoglobin mass index (MCH), white blood cells (WBCs), and neutrophil concentration were observed in subjects in the acute phase of ischemic stroke
The biochemical analysis in the acute stroke group (A) showed significantly higher values of TSH and glycemia followed by significantly lower serum potassium concentration as compared with the control group, all of these values were within the normal range

Summary

Introduction

Cardiovascular disease (CVD) remains among the most common causes of morbidity and mortality, as reported worldwide annually. In Europe, almost half of fatal cases have been directly connected with CVD [1]. In 70–80% of cases, it is caused by cerebral ischemia [3] and is increasingly referred to as “acute cerebral syndrome”, indicating its similarity to acute coronary syndromes. The detection of biochemical markers of vascular-derived brain damage should have a diagnostic and prognostic meaning, similar to that of myocardial infarction and heart failure (e.g., troponin (Tn) and N-terminal natriuretic peptide type B (NT-proBNP)). Since biomarkers must be characterized by certain features [4,5], there is still a lack of substances that could be used as reliable indicators of acute central nervous system (CNS) ischemia, which could allow quick performance of diagnostics and appropriate treatment [6]

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