Clinical significance of plasma VEGF value in ischemic stroke - research for biomarkers in ischemic stroke (REBIOS) study

Matsuo, Ryu; Ago, Tetsuro; Kamouchi, Masahiro; Kuroda, Junya; Kuwashiro, Takahiro; Hata, Jun; Sugimori, Hiroshi; Fukuda, Kenji; Gotoh, Seiji; Makihara, Noriko; Fukuhara, Mikio; Awano, Hideto; Isomura, Tetsu; Suzuki, Kazuhiro; Yasaka, Masahiro; Okada, Yasushi; Kiyohara, Yutaka; Kitazono, Takanari

doi:10.1186/1471-2377-13-32

Cited by 100 publications

(91 citation statements)

References 23 publications

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“…Notably, VEGF-A has been associated with an increased risk of ischaemic stroke in the Framingham Heart Study 27 28. Studies of acute stroke have shown increased plasma VEGF-A levels at the time of stroke events and correlations between VEGF-A and worse long-term prognosis 29. In contrast to VEGF-D and AF-related stroke, the pathophysiological mechanisms for the association between VEGF-A and stroke are most likely different and could possibly be explained by hypoxia-induced expression of VEGF-A 29…”

Section: Discussionmentioning

confidence: 99%

Increased vascular endothelial growth factor D is associated with atrial fibrillation and ischaemic stroke

Berntsson

Smith

Johnson

et al. 2018

Heart

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ObjectiveVascular endothelial growth factor D (VEGF-D) has important functions in lymphangiogenesis and angiogenesis. High plasma levels of VEGF-D have been associated with incidence of heart failure. The association of VEGF-D with atrial fibrillation (AF) and stroke is unclear and we hypothesised that VEGF-D could also be associated with incidence of AF and ischaemic stroke.MethodsVEGF-D was measured in fasting blood samples of 4689 subjects (40% men) without a history of AF from the Malmö Diet and Cancer Study, a prospective, population-based study in Sweden. Median age was 58 years (range 46–68). Cox regression analyses, adjusted for multiple risk factors, was used to assess AF and ischaemic stroke risk in relation to VEGF-D levels.ResultsDuring a median follow-up time of 20.6 years, there were 637 cases of incident AF and 322 cases of first ischaemic stroke. After adjustment, VEGF-D was significantly associated with AF (HR 1.13(95% CI 1.04 to 1.23) per 1 SD increase) and ischaemic stroke (HR 1.14(95% CI 1.02 to 1.28) per 1 SD). The association with ischaemic stroke was explained by an increased incidence of AF-related stroke. HRs per 1 SD were 1.34 (95% CI 1.04 to 1.71) for AF-related ischaemic stroke and 1.04 (95% CI 0.90 to 1.19) for ischaemic stroke without AF.ConclusionsIncreased VEGF-D concentrations were associated with AF and ischaemic stroke. The relationship with ischaemic stroke was more pronounced in subjects with a diagnosis of AF.

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Section: Discussionmentioning

confidence: 99%

Increased vascular endothelial growth factor D is associated with atrial fibrillation and ischaemic stroke

Berntsson

Smith

Johnson

et al. 2018

Heart

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“…Research by Matsuo et al argued that higher VEGF levels in atherothrombotic stroke, therefore, were associated with better outcomes than the low levels of VEGF in post-acute thrombotic stroke. Further, the research found that high levels of VEGF in embolic stroke were associated with worse outcomes 16. In this current study, evaluation of patients’ clinical conditions was not performed.…”

Section: Discussionmentioning

confidence: 82%

Thicker carotid intima-media thickness and increased plasma VEGF levels suffered by post-acute thrombotic stroke patients

Yueniwati¹,

Darmiastini²,

Arisetijono³

2016

IJGM

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Background and objectivesAtherosclerosis causes reduction of the oxygen supply to structures in the far arterial wall, provoking the release of factors that drive angiogenesis of vasa vasorum, including VEGF. Other studies have revealed the inflammatory response in atherosclerosis and the role of platelet factor 4 (PF4) as an anti-angiogenic chemokine through the inhibition of VEGF. This cross-sectional study aims at measuring the effect of atherosclerosis assessed through carotid intima-media thickness (CIMT) against plasma VEGF levels in patients with post-acute thrombotic stroke.Materials and methodsCIMT was assessed sonographically using GE Logiq S6 with 13 MHz frequency linear probe. VEGF-A plasma levels were measured using enzyme-linked immunosorbent assay (ELISA) method. Differences among variables were compared statistically. The data were analyzed using Pearson correlation.ResultsA total of 25 patients with post-acute thrombotic stroke were identified in days 7 to 90. CIMT thickening was indicated in 88% of patients (1.202 ± 0.312 mm), while an increase in plasma VEGF was identified in all patients (178.28 ± 93.96 ng/mL). There was no significant correlation between CIMT and plasma VEGF levels in patients with post-acute thrombotic stroke (p=0.741). A significant correlation was recognized between CIMT and total cholesterol (p=0.029) and low-density lipoprotein (p=0.018).ConclusionThere were no significant correlations between CIMT and plasma VEGF levels in patients with post-acute thrombotic stroke. However, plasma VEGF increased in patients with thrombotic stroke. CIMT measurement is a promising noninvasive modality to assess the vascular condition of patients with stroke and diabetes, while plasma VEGF cannot specifically assess vascular condition as it can be triggered by ischemic conditions in tissues of the whole body.

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“…It has been observed that transplantation of bone marrow mesenchymal stem cells into ischemic brain resulted in gain of coordinated function in rats due to bone marrow cell soluble factor release, resulting in inhibited scar formation, increased angiogenesis and neuronal commitment [44,45]. Matsuo et al [46] posited that increased plasma VEGF values last for at least 90 days in all stroke subtypes, and the clinical significance varies for different stroke types. It was found that the severely affected group had a high mean VEGF of 592.1 versus 487.6 pg/ml (p = 0.76), without any statistically significant improvement between groups 1 and 2 (fig.…”

Section: Discussionmentioning

confidence: 99%

Paracrine Mechanisms of Intravenous Bone Marrow-Derived Mononuclear Stem Cells in Chronic Ischemic Stroke

Bhasin

Srivastava

Mohanty

et al. 2016

Cerebrovasc Dis Extra

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Background: The emerging role of stem cell technology and transplantation has helped scientists to study their potential role inneural repair and regeneration.The fateof stem cells is determined by their niche, consisting of surrounding cells and the secreted trophic growth factors. This interim report evaluates the safety, feasibility and efficacy (if any) of bone marrow-derived mononuclear stem cells (BM-MNC) in chronic ischemic stroke by studying the release of serum vascular endothelial growth factor (VEGF) and brain-derived neurotrophic growth factor (BDNF). Methods: Twenty stroke patients and 20 age-matched healthy controls were recruited with the following inclusion criteria: 3 months to 1.5 years from the index event, Medical Research Council (MRC) grade of hand muscles of at least 2, Brunnstrom stage 2-5, conscious, and comprehendible. They were randomized to one group receiving autologous BM-MNC (mean 60-70 million) and to another group receiving saline infusion (placebo). All patients were administered a neuromotor rehabilitation regime for 8 weeks. Clinical assessments [Fugl Meyer scale (FM), modified Barthel index (mBI), MRC grade, Ashworth tone scale] were carried out and serum VEGF and BDNF levels were assessed at baseline and at 8 weeks. Results: No serious adverse events were observed during the study. There was no statistically significant clinical improvement between the groups (FM: 95% CI 15.2-5.35, p = 0.25; mBI: 95% CI 14.3-4.5, p = 0.31). VEGF and BDNF expression was found to be greater in group 1 compared to group 2 (VEGF: 442.1 vs. 400.3 pg/ml, p = 0.67; BDNF: 21.3 vs. 19.5 ng/ml) without any statistically significant difference. Conclusion: Autologous mononuclear stem cell infusion is safe and tolerable by chronic ischemic stroke patients. The released growth factors (VEGF and BDNF) in the microenvironment could be due to the paracrine hypothesis of stem cell niche and neurorehabilitation regime.

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Clinical significance of plasma VEGF value in ischemic stroke - research for biomarkers in ischemic stroke (REBIOS) study

Cited by 100 publications

References 23 publications

Increased vascular endothelial growth factor D is associated with atrial fibrillation and ischaemic stroke

Increased vascular endothelial growth factor D is associated with atrial fibrillation and ischaemic stroke

Thicker carotid intima-media thickness and increased plasma VEGF levels suffered by post-acute thrombotic stroke patients

Paracrine Mechanisms of Intravenous Bone Marrow-Derived Mononuclear Stem Cells in Chronic Ischemic Stroke

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