Plasma Proteomics Of Patients With Post-stroke Depression Based On ITRAQ

BackgroundPost-stroke depression (PSD) is the most common psychiatriccomplication facing stroke survivors and has been associated with increaseddistress, physical disability, poor rehabilitation, and suicidal ideation.However, the pathophysiological mechanisms underlying PSD remainunknown, and no objective laboratory-based test available to aid PSDdiagnosis or monitor progression.ObjectiveIn this study, an iTRAQ-based proteomic approach was employed toprofile plasma samples from PSD, stroke and healthy control subjects inorder to identify plasma protein biomarker candidates for PSD. Thus providethe basis for the diagnosis, prevention, pathogenesis, and treatment of PSD.MethodsHere, a comparative proteomic study was performed to identifydifferentially expressed proteins in plasma samples obtained from PSD,stroke, and healthy control subjects. Samples from the three groups wereimmunodepleted of fourteen high-abundance proteins, labeled with isobarictags for relative and absolute quantitation, and then analyzed bymulti-dimensional liquid chromatography-tandem mass spectrometry. Theproteomic results were further validated by immunoblotting and analyzed with Database for Annotation, Visualization, and Integrated DiscoveryBioinformatics Resources.ResultsThe results demonstrate that the functions of the significantlydifferentiated proteins are primarily involved in lipid metabolism andimmunoregulation. Six proteins associated with these processes–apolipoprotein A-IV (apoA-IV), apolipoprotein C-II (apoC-II), C-reactiveprotein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein(LRG)–were selected for Western blotting validation. ApoA-IV expressionwas significantly upregulated in PSD as compared to stroke subjects.ApoC-II, LRG, and CRP expression were significantly downregulated inboth PSD and HC subjects relative to stroke subjects. Gelsolin andhaptoglobin expression were significantly dysregulated across all threegroups with the following expression profiles: gelsolin, healthy control>PSD> stroke subjects; haptoglobin, stroke> PSD> healthy control subjects.ConclusionAs gelsolin and haptoglobin display unique tiered expression profiles,the combination of increased gelsolin levels accompanied by decreasedhaptoglobin levels shows promise as a diagnostic biomarker panel forincreased PSD risk in post-stroke patients.