Discovery of Prognostic Biomarker Candidates of Lacunar Infarction by Quantitative Proteomics of Microvesicles Enriched Plasma

Abstract

BackgroundLacunar infarction (LACI) is a subtype of acute ischemic stroke affecting around 25% of all ischemic stroke cases. Despite having an excellent recovery during acute phase, certain LACI patients have poor mid- to long-term prognosis due to the recurrence of vascular events or a decline in cognitive functions. Hence, blood-based biomarkers could be complementary prognostic and research tools.Methods and FindingPlasma was collected from forty five patients following a non-disabling LACI along with seventeen matched control subjects. The LACI patients were monitored prospectively for up to five years for the occurrence of adverse outcomes and grouped accordingly (i.e., LACI-no adverse outcome, LACI-recurrent vascular event, and LACI-cognitive decline without any recurrence of vascular events). Microvesicles-enriched fractions isolated from the pooled plasma of four groups were profiled by an iTRAQ-guided discovery approach to quantify the differential proteome. The data have been deposited to the ProteomeXchange with identifier PXD000748. Bioinformatics analysis and data mining revealed up-regulation of brain-specific proteins including myelin basic protein, proteins of coagulation cascade (e.g., fibrinogen alpha chain, fibrinogen beta chain) and focal adhesion (e.g., integrin alpha-IIb, talin-1, and filamin-A) while albumin was down-regulated in both groups of patients with adverse outcome.ConclusionThis data set may offer important insight into the mechanisms of poor prognosis and provide candidate prognostic biomarkers for validation on larger cohort of individual LACI patients.

Uncovering Neurodegenerative Protein Modifications via Proteomic Profiling

“…Despite this ability to yield useful data on the molecular pathology of neurodegeneration, use of these techniques is complicated by the extreme complexity of CNS tissues, which restricts the characterization of low-abundance proteins (Choudhary & Grant, 2004). Another drawback is the relative expense of the stable isotope labeling reagents and instrumentation required, which necessitates the pooling of samples from multiple individual subjects (Datta, Chen, & Sze, 2014;Datta et al, 2011Datta et al, , 2010Datta, Qian, et al, 2014;Dutta, Yan, Lim, Tam, & Sze, 2014). Yet another challenge associated with the use of quantitative proteomics to analyze brain tissues is the inability to assign the identified and characterized proteins to specific cell types in the affected tissues.…”

The Infarct Shape Predicts Progressive Motor Deficits in Patients with Acute Lacunae-sized Infarctions in the Perforating Arterial Territory

“…Acute isolated infarction in the territory of a single penetrating artery, which is caused by atherosclerosis at the proximal segment of the penetrating arteries or lipohyalinotic degeneration of arterioles, is called PAD, which can be presented with a giant lacunar infarction. Lacunar infarction is a subtype of ischemic stroke that accounts for approximately 25% of all ischemic stroke cases with a higher prevalence in the south Asian population (4)(5)(6). Diverse morphologic patterns of lacunae-sized ischemic infarction could be detected by diffusion-weighted imaging (DWI) scans in the perforating arterial territory.…”

Analysis of the plasma proteome using iTRAQ and TMT‐based Isobaric labeling

“…Larkin et al implemented HILIC in a variation of the three dimensional depletion‐free strategy initially described by Al‐Daghri, notably identifying in the order of a thousand proteins . Another alternative using anion exchange columns for fractionation is Electrostatic Repulsion‐Hydrophilic Interaction Chromatography (ERLIC), which was used by Datta et al in a study where they enriched plasma mircovesicles in a study of lacunar infarction …”