Dataset Information

Platelets Proteomic Profiles of Acute Ischemic Stroke Patients.

ABSTRACT: Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets' tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight into the proteins that are involved in the platelets' activation response during ischemic stroke. It could be argued that this study lays the foundation for future mechanistic studies.

SUBMITTER: Cevik O

PROVIDER: S-EPMC4919045 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Platelets Proteomic Profiles of Acute Ischemic Stroke Patients.

Cevik Ozge O Baykal Ahmet Tarik AT Sener Azize A

PloS one 20160623 6

Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses ...[more]

PMID: 27336623

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Project description:BACKGROUND:Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is a devastating cerebrovascular disorder, which could benefit from collateral circulation. Proteins associated with acute LVO pathogenesis and endothelial function may appear in blood samples of AIS patients due to LVO, thus permitting development of blood-based biomarkers for its diagnosis and prognosis. METHODS:This study is a single-center, retrospective, observational case-control trial. Consecutive patients who presented at the Department of Neurology of Tongji Hospital were recruited from July 2016 to April 2018. In the discovery phase, a proteomic approach with iTRAQ-based LC-MS/MS was used to investigate the altered proteomic pattern in plasma from patients with AIS due to LVO. In the validation study, Western blots was used to identify biomarkers associated with stroke diagnosis as well as their prognostic value associated with different collateral statuses. RESULTS:For this exploratory study, the proteomic analysis of plasma from 40 patients with AIS due to LVO and 20 healthy controls revealed seven differentially expressed proteins with a 1.2/0.83-fold or greater difference between groups. The four elevated proteins, PPBP (1.58 ± 0.78 vs 0.98 ± 0.37; P < 0.001), THBS1 (1.13 ± 0.88 vs 0.43 ± 0.26; P < 0.001), LYVE1 (1.61 ± 0.55 vs 0.97 ± 0.50; P < 0.001), and IGF2 (1.19 ± 0.42 vs 0.86 ± 0.24; P < 0.001), were verified by Western blots analysis in an independent cohort including 33 patients and 33 controls. A strong interaction was observed between the four-protein panel and the diagnosis of AIS due to LVO (AUC 0.947; P < 0.001). Furthermore, IGF2, LYVE1, and THBS1 were closely associated with collateral status (IGF2 0.115, 95% CI 0.016-0.841, P = 0.033; LYVE1 0.183, 95% CI 0.036-0.918, P = 0.039; THBS1 4.257, 95% CI 1.273-14.228, P = 0.019), and proved to be independent predictors of good outcome (IGF2 0.115, 95% CI 0.015-0.866, P = 0.036; LYVE1 0.028, 95% CI 0.002-0.334, P = 0.005; THBS1 3.294, 95% CI 1.158-9.372, P = 0.025) at a 3-month follow-up. CONCLUSIONS:The identified 4-biomarker panel could provide diagnostic aid to the existing imaging modalities for AIS due to LVO, and the prognostic value of IGF2, LYVE1, and THBS1 was proved in predicting functional outcomes related to collateral status. Trial registration ClinicalTrials.gov NCT03122002. Retrospectively registered April 20, 2017. URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/NCT03122002?term=NCT+03122002&rank=1.

Project description:Background and Purpose- The location of the thrombus as observed on first digital subtraction angiography during endovascular treatment may differ from the initial observation on initial noninvasive imaging. We studied the incidence of thrombus dynamics, its impact on patient outcomes, and its association with intravenous thrombolytics. Methods- We included patients from the MR CLEAN registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke) with an initial target occlusion on computed tomography angiography located in the intracranial internal carotid artery, M1, or M2. The conventional angiography target occlusion was defined during endovascular treatment. Thrombus dynamics were classified as growth, stability, migration, and resolution. The primary outcome was functional outcome at 90 days (modified Rankin Scale). The secondary outcomes were successful and complete reperfusion (extended treatment in cerebral infarction scores of 2b-3 and 3, respectively). Results- The analysis included 1349 patients. Thrombus migration occurred in 302 (22%) patients, thrombus growth in 87 (6%), and thrombus resolution in 39 (3%). Intravenous treatment with alteplase was associated with more thrombus migration (adjusted odds ratio, 2.01; CI, 1.29-3.11) and thrombus resolution (adjusted odds ratio, 1.85; CI, 1.22-2.80). Thrombus migration was associated with a lower chance of complete reperfusion (adjusted odds ratio, 0.57; CI, 0.42-0.78) and successful reperfusion (adjusted odds ratio, 0.74; CI, 0.55-0.99). In the subgroup of patients with M1 initial target occlusion, thrombus migration was associated with better functional outcome (adjusted common odds ratio, 1.49; CI, 1.02-2.17), and there was a trend towards better functional outcome in patients with thrombus resolution (adjusted common odds ratio, 2.23; CI, 0.93-5.37). Conclusions- In patients with acute ischemic stroke, thrombus location regularly changes between computed tomography angiography and digital subtraction angiography. Administration of intravenous alteplase increases the chance of thrombus migration and resolution. Thrombus migration is associated with better functional outcome but reduces the rate of complete reperfusion.

Project description:Plasma total homocysteine (tHcy) is a risk factor for ischemic stroke (IS) but its relationship with IS outcome is uncertain. Moreover, previous studies underrepresented older IS patients, although risk of both hyperhomocysteinemia and IS increases with age. We investigated whether, in elderly patients with acute IS, tHcy measured on admission to the Stroke Unit (SU) is an independent predictor of SU discharge outcomes.Data are for 644 consecutive patients aged 80.3 ± 8.7 years, admitted to an Italian SU with diagnosis of acute IS. Plasma tHcy was measured on SU admission. Investigated outcomes included mortality during SU stay and poor functional status (modified Rankin Scale score ≥3) at SU discharge for survivors. The association of plasma tHcy with the study outcomes was assessed using Odds Ratios (OR) and their corresponding 95% confidence intervals (95%CI) from logistic regression models adjusted for demographics, pre-stroke features, IS severity, and laboratory data on SU admission (serum C-reactive protein, serum albumin, and renal function).Median plasma tHcy was 16.7 μmol/L (interquartile range, 13.0-23.3 μmol/L). Outcome incidence was 5.3% for mortality and 49.7% for poor functional status. Plasma tHcy was unrelated to mortality in both univariate and multivariable-adjusted analyses. Conversely, plasma tHcy was associated with poor functional status of survivors in univariate analyses (P = 0.014). Multivariable-adjusted analyses showed that, compared to normal homocysteinemia (tHcy <16 μmol/L), risk of being discharged with poor functional status significantly increased for moderate (tHcy ≥30 mol/L) but not mild (16.0-29.9 μmol/L) hyperhomocysteinemia.In elderly patients with acute IS, high admission plasma tHcy is unrelated to mortality during SU stay but is an independent predictor of poor functional status at SU discharge in survivors. The association, however, is limited to patients with moderate hyperhomocysteinemia.

Project description:Rationale: Remote ischemic perconditioning during cerebral ischemia (RIPerC) refers to the application of brief episodes of transient limb ischemia commonly to a limb, it represents a new safe, simple and low-cost paradigm in neuroprotection. Aim and/or Hypothesis: To evaluate the effects of RIPerC on acute ischemic stroke (AIS) patients, applied in the ambulance, to improve functional outcomes compared with standard of care. Sample Size Estimates: A sample size of 286 patients in each arm achieves 80% power to detect treatment differences of 14% in the outcome, using a two-sided binomial test at significance level of 0.05, assuming that 40% of the control patients will experience good outcome and an initial misdiagnosis rate of 29%. Methods and Design: We aim to conduct a multicentre study of pre-hospital RIPerC application in AIS patients. A total of 572 adult patients diagnosed of suspected clinical stroke within 8 h of symptom onset and clinical deficit >0 according to prehospital rapid arterial occlusion evaluation (RACE) scale score will be randomized, in blocks of size 4, to RIPerC or sham. Patients will be stratified by RACE score scale. RIPerC will be started in the ambulance before hospital admission and continued in the hospital if necessary. It will consist of five cycles of electronic tourniquet inflation and deflation (5 min each). The cuff pressure for RIPerC will be 200 mmHg during inflation. Sham will only simulate vibration of the device. Study Outcome(s): The primary outcome will be the difference in the proportion of patients with good outcomes as defined by a mRS score of 2 or less at 90 days. Secondary outcomes to be monitored will include early neurological improvement rate, treatment related serious adverse event rates, size of the infarct volume, symptomatic intracranial hemorrhage, metabolomic and lipidomic response to RIPerC and Neuropsychological evaluation at 90 days. Discussion: Neuroprotective therapies could not only increase the benefits of available reperfusion therapies among AIS patients but also provide an option for patients who are not candidates for these treatments. REMOTE-CAT will investigate the clinical benefit of RIC as a new neuroprotective strategy in AIS. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03375762.

Dataset Information

Platelets Proteomic Profiles of Acute Ischemic Stroke Patients.

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Platelets Proteomic Profiles of Acute Ischemic Stroke Patients.

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