New Candidates for Biomarkers and Drug Targets of Ischemic Stroke—A First Dynamic LC-MS Human Serum Proteomic Study

Abstract

(1) Background: The aim of this dynamic-LC/MS-human-serum-proteomic-study was to identify potential proteins-candidates for biomarkers of acute ischemic stroke, their changes during acute phase of stroke and to define potential novel drug-targets. (2) Methods: A total of 32 patients (29–80 years) with acute ischemic stroke were enrolled to the study. The control group constituted 29 demographically-matched volunteers. Subjects with stroke presented clinical symptoms lasting no longer than 24 h, confirmed by neurological-examination and/or new cerebral ischemia visualized in the CT scans (computed tomography). The analysis of plasma proteome was performed using LC-MS (liquid chromatography–mass spectrometry). (3) Results: Ten proteins with significantly different serum concentrations between groups volunteers were: complement-factor-B, apolipoprotein-A-I, fibronectin, alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, heat-shock-cognate-71kDa protein/heat-shock-related-70kDa-protein-2, thymidine phosphorylase-2, cytoplasmic-tryptophan-tRNA-ligase, ficolin-2, beta-Ala-His-dipeptidase. (4) Conclusions: This is the first dynamic LC-MS study performed on a clinical model which differentiates serum proteome of patients in acute phase of ischemic stroke in time series and compares to control group. Listed proteins should be considered as risk factors, markers of ischemic stroke or potential therapeutic targets. Further clinical validation might define their exact role in differential diagnostics, monitoring the course of the ischemic stroke or specifying them as novel drug targets.

Proteomic investigations of acute ischemic stroke in animal models: a narrative review

“…For example, in a longitudinal biomarker and drug target study, increases in CFB, AHSG, FN1, and APOA1 were observed in human serum with the progression of AIS. [5] Integration of transcriptomics and proteomics identified 76 proteins that were differentially expressed in the ischemic brain. Of these, Gadd45g and Ctnnd2 were identified as promising blood biomarkers for AIS prognosis and diagnosis after validation using Parallel Reaction Monitoring (PRM)-targeted proteomics and the Nanostring nCounter assay in a new cohort of MCAO mice.…”

“…Research on human AIS is limited owing to high death rate, unexpected onset, and severity, mainly focusing on diagnostic/prognostic biomarker discovery. [2][3][4][5][6][7][8][9][10][11][12] Therapeutic targets are commonly generated and characterized preclinically using various in vitro and in vivo models. Simple systems like cell models are suitable for high-throughput screenings and function interrogation.…”

Association of low ficolin-2 concentration in cord serum with respiratory distress syndrome in preterm newborns

“…Ficolin-2 is considered to be an important factor of innate immunity. Several reports suggested its association not only with infections but also with non-infectious diseases and its potential application as a prognostic marker ( 22 – 24 ). In this study, we examined ficolin-2 levels in cord-blood serum of preterm neonates in the context of prematurity-associated complications and its possible usefulness for their diagnosis.…”