Abstract
Systematic profiling of a larger portion of circulating plasma proteome provide opportunities for unbiased discovery of novel markers to improve diagnostic, therapeutic, or predictive accuracy. This study aimed to identify differentially expressed proteins (DEPs) in plasma that could provide overall insight into the molecular changes of both H- type hypertension (HH) and HH-related acute ischemic stroke (AIS). This study used an iTRAQ-based LC-MS/MS proteomics approach to screen for plasma DEPs in HH patients with and without AIS, and controls. After excluding highly abundant plasma proteins, more than 600 proteins, and their relative levels, were identified. Of these, 26 DEPs, each showing > 1.2-fold change, were identified in HH and HH-related AIS patients compared with controls. Bioinformatics analysis revealed that these DEPs were enriched in 21 functional gene ontology items; “blood coagulation” was the most predominant pathway showing enrichment. Of these, eight DEPs were located in the hub position of networks involved with protein-protein interactions. AT-3, CRP, ApoB, and AHSG were further validated in each group by enzyme-linked immune sorbent assays. Comparing HH-related AIS with HH, the areas under the curve for AT-3, CRP, ApoB, and AHSG were 0.698, 0.892, 0.626, and 0.847, respectively. This proteomic profiling study provided enhanced pathophysiological understanding of the regulatory processes involved in coagulation, inflammation, and metabolism, and identified a panel of novel biomarkers for detecting HH-related AIS during its pre-stroke stage.
Highlights
Stroke, a multifactorial disease, is one of the leading health issues with permanent physical and neurological disabilities worldwide, and results in high morbidity and mortality rates [1, 2]
This study used an isolated tags for relative and absolute quantitation (iTRAQ)-based LC-MS/MS proteomics approach to screen for plasma differentially expressed proteins (DEPs) in H- type hypertension (HH) patients with and without acute ischemic stroke (AIS), and controls
Using an iTRAQ-based LC-MS/MS approach, we identified a series of surrogate plasma biomarkers which correlated with the pathophysiological changes of both HH and HH- related AIS
Summary
A multifactorial disease, is one of the leading health issues with permanent physical and neurological disabilities worldwide, and results in high morbidity and mortality rates [1, 2]. Despite progress in acute treatment protocols for ischemic stroke, prevention remains the most effective approach to reduce impact upon personal and public health [3]. Interactions between inflammation, immune reaction, and oxidative damage are responsible for the development of atherosclerotic ischemic stroke by hyperhomocysteinemia [5,6,7], but the underlying pathophysiological pathways leading from HH to acute ischemic stroke (AIS) remain poorly understood. More potent biomarkers are needed for the detection of HHrelated AIS during its pre-stroke stage when it can be intervened more effectively
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