Predictive value of thrombospondin-1 for outcomes in patients with acute ischemic stroke

Gao, Jianbo; Tang, Weidong; Wang, Hongxiang; Xu, Yan

doi:10.1016/j.cca.2015.08.014

Cited by 29 publications

(30 citation statements)

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“…Thrombospondin 1 (THBS1) was first isolated from human blood platelets as a thrombin-sensitive protein [14]. THBS1 is a potent regulator of angiogenesis that functions to concurrently inhibit endothelial cell migration and the release of vascular endothelial growth factor from the extracellular matrix [11].…”

Section: Discussionmentioning

confidence: 99%

“…THBS1 is a potent regulator of angiogenesis that functions to concurrently inhibit endothelial cell migration and the release of vascular endothelial growth factor from the extracellular matrix [11]. Cerebral THBS1 expression is upregulated in experimental focal cerebral ischemia [15] and the circulating THBS1 were elevated in patients with ischemic stroke [14]. …”

Section: Discussionmentioning

confidence: 99%

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Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion

et al. 2019

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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 NCT 03122002. Retrospectively registered April 20, 2017. URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/NCT03122002?term=NCT+03122002&rank=1 Electronic supplementary material The online version of this article (10.1186/s12967-019-1962-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion

et al. 2019

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“…Elevated plasma concentrations of TSP-1 has been found in patients with coronary artery disease, diabetes mellitus [31], peripheral artery disease [32] and stroke [33]. Thus, elevated TSP-1 concentrations may be a biomarker of cardiovascular disease states.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D supplementation lowers thrombospondin-1 levels and blood pressure in healthy adults

et al. 2017

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IntroductionVitamin D insufficiency, defined as 25-hydroxyvitamin D (25(OH)D) levels < 75nmol/L is associated with cardio-metabolic dysfunction. Vitamin D insufficiency is associated with inflammation and fibrosis, but it remains uncertain whether these anomalies are readily reversible. Therefore, we aimed to determine the effects of vitamin D supplementation on markers of: 1) nitric oxide (NO) signaling, 2) inflammation, and 3) fibrosis, in healthy volunteers with mild hypovitaminosis.MethodsHealthy volunteers (n = 35) (mean age: 45 ± 11 years) with 25(OH)D levels <75nmol/L, received vitamin D supplementation (Ostelin ® capsules 2000IU) for 12 weeks. Resting systolic and diastolic blood pressures (BP) were assessed. Routine biochemistry was examined. Plasma concentrations of asymmetric dimethylarginine (ADMA), thrombospondin-1 (TSP-1), plasminogen activator inhibitor-1 (PAI-1), hs-CRP, activin-A, and follistatin-like 3 (FSTL3) were quantitated.ResultsVitamin D administration for 12 weeks significantly increased 25-(OH)D levels (48.8 ± 16 nmol/L to 100.8 ± 23.7 nmol/L, p<0.001). There was significant lowering of systolic and diastolic BP, while there was no significant change in lipid profiles, or fasting insulin. Plasma concentrations of ADMA, hs-CRP, PAI-1, activin A, and FSTL-3 did not change with vitamin D supplementation. However, there was a marked reduction of TSP-1 (522.7 ± 379.8 ng/mL vs 206.7 ± 204.5 ng/mL, p<0.001).ConclusionsVitamin D supplementation in vitamin D insufficient, but otherwise healthy individuals markedly decreased TSP-1 levels and blood pressure. Since TSP-1 suppresses signaling of NO, it is possible that the fall in BP is engendered by restoration of NO effect.

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“…Notably, histopathological analysis demonstrates poststroke angiogenesis in patients, and the degree of angiogenesis correlates with better functional outcome and longer survival following stroke . Further, elevation of anti‐angiogenesis factors in blood (eg, thrombospondin‐1) predicts poor long‐term outcome and is associated with higher mortality …”

Section: Discussionmentioning

confidence: 99%

Modulation of the peri‐infarct neurogliovascular function by delayed COX‐1 inhibition

Lake

Mester

Thomason

et al. 2016

Magnetic Resonance Imaging

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Predictive value of thrombospondin-1 for outcomes in patients with acute ischemic stroke

Cited by 29 publications

References 29 publications

Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion

Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion

Vitamin D supplementation lowers thrombospondin-1 levels and blood pressure in healthy adults

Modulation of the peri‐infarct neurogliovascular function by delayed COX‐1 inhibition

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