Dataset Information

Interplay between VEGF and Nrf2 regulates angiogenesis due to intracranial venous hypertension.

ABSTRACT: Venous hypertension(VH) plays an important role in the pathogenesis of cerebral arteriovenous malformations (AVMs) and is closely associated with the HIF-1?/VEGF signaling pathway. Nuclear factor erythroid 2-related factor 2(Nrf2) significantly influences angiogenesis; however, the interplay between Nrf2 and VEGF under VH in brain AVMs remains unclear. Therefore, our study aimed to investigate the interplay between Nrf2 and VEGF due to VH in brain AVMs. Immunohistochemistry indicated that Nrf2 and VEGF were highly expressed in human brain AVM tissues. In vivo, we established a VH model in both wild-type (WT) and siRNA-mediated Nrf2 knockdown rats. VH significantly increased the expression of Nrf2 and VEGF. Loss of Nrf2 markedly inhibited the upregulation of VEGF, as determined by Western blot analysis and qRT-PCR. In vitro, primary brain microvascular endothelial cells (BMECs) were isolated from WT and Nrf2^-/- mice, and a VEGF-Nrf2 positive feed-back loop was observed in BMECs. By trans well assay and angiogenesis assay, Nrf2 knockout significantly inhibited the migration and vascular tube formation of BMECs. These findings suggest that the interplay between Nrf2 and VEGF can contribute to VH-induced angiogenesis in brain AVMs pathogenesis.

SUBMITTER: Li L

PROVIDER: S-EPMC5116754 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interplay between VEGF and Nrf2 regulates angiogenesis due to intracranial venous hypertension.

Li Liwen L Pan Hao H Wang Handong H Li Xiang X Bu Xiaomin X Wang Qiang Q Gao Yongyue Y Wen Guodao G Zhou Yali Y Cong Zixiang Z Yang Youqing Y Tang Chao C Liu Zhengwei Z

Scientific reports 20161121

Venous hypertension(VH) plays an important role in the pathogenesis of cerebral arteriovenous malformations (AVMs) and is closely associated with the HIF-1α/VEGF signaling pathway. Nuclear factor erythroid 2-related factor 2(Nrf2) significantly influences angiogenesis; however, the interplay between Nrf2 and VEGF under VH in brain AVMs remains unclear. Therefore, our study aimed to investigate the interplay between Nrf2 and VEGF due to VH in brain AVMs. Immunohistochemistry indicated that Nrf2 a ...[more]

PMID: 27869147

Similar Datasets

Project description:Background and purposeCerebral venous thrombosis (CVT) is a special cerebrovascular disease that accounts for around 0.5%-1.0% of all strokes and often occurs in younger adults. Intracranial hypertension is the most frequent symptom of acute CVT due to venous occlusion. This study aimed to ascertain the risk factors for intracranial hypertension after CVT and to investigate whether intracranial hypertension at diagnosis may affect patient outcomes.MethodsWe performed a retrospective cohort analysis of all patients treated for acute/subacute CVT at our department between 2018 and 2021. Logistic regression analysis was performed to identify potential risk factors associated with intracranial hypertension after CVT and clinical outcomes at the 6-month follow-up.ResultsA total of 293 acute/subacute CVT survivors were eligible for inclusion, with 245 patients (83.60%) experiencing concomitant intracranial hypertension at diagnosis. In the multivariable regression analysis, hereditary thrombophilia (OR 2.210, 95% CI 1.148-4.254, p = 0.018) and thrombosis location of superior sagittal sinus (SSS) and right lateral sinus (LS) (OR 4.115, 95% CI 1.880-9.010, p = 0.000) were independently associated with intracranial hypertension. 83.67% of patients with intracranial hypertension after CVT had favorable functional outcomes (mRS score, 0-2), whereas they more often had residual visual impairment (15.51% vs. 4.17%, p = 0.036) at follow-up. The risk factors for residual visual impairment were papilledema (OR 2.971, 95% CI 1.231-7.170, p = 0.015) and visual disturbances at diagnosis (OR 2.869, 95% CI 1.123-7.327, p = 0.028), thrombosis location (SSS and right LS [OR 10.811, 95% CI 4.208-27.773, p = 0.000]; SSS and left LS [OR 3.139, 95% CI 1.409-6.995, p = 0.005]), and CVT recurrence (OR 4.763, 95% CI 1.556-14.584, p = 0.006).ConclusionsIntracranial hypertension is the most common clinical symptom of acute CVT. At follow-up, patients with intracranial hypertension after CVT were more prone to develop residual visual impairment.

Project description:PURPOSE:Magnetic resonance venography (MRV) has not been validated in pre-operative planning of the dural venous sinus stenting (VSS) among idiopathic intracranial hypertension (IIH) patients. We aim to prospectively evaluate dural venous sinus measurement in IIH patient population on two-dimensional time-of-flight (2D-TOF) MRV and Three-dimensional contrast-enhanced (3D-CE) MRV acquisitions and compare them against real-time endoluminal measurements with intravascular ultrasound (IVUS), served as the reference. MATERIALS AND METHODS:The study has been approved by the Weill Cornell Medicine institutional review board. All patients signed written informed consent approved by IRB. Prospective evaluation of forty-five consecutive IIH patients treated with VSS at our institution were evaluated. Patients with pre-stent magnetic resonance venography (MRV) ? 6-months of VSS and intravascular ultrasound (IVUS) during VSS constituted the study population. Maximum diameter (in mm), Area (in cm2) and Perimeter (in cm) were measured at posterior 1/3rd of superior sagittal sinus (SSS), proximal transverse sinus (PTS), proximal sigmoid sinus (PSS) and mid sigmoid sinus (MSS) on 2D-TOF-MRV, 3D-CE-MRV and IVUS. Statistical analysis performed using box and whisker plots, Bland-Altman analysis and paired sample t-test. RESULTS:Twenty (n = 20) patients constituted our study population. The mean age was 30±11 years (7-59 years) and 18 out of 20 were female patients. Mean weight and BMI (range) were 86.3±18.3 kilograms (30.8-107.5 kgs) and 32.9±6.8 kg/M2 (16.4-48.3kg/M2) respectively. The CE-MRV significantly oversized the cerebral venous sinuses compared to TOF-MRV (Dmax: +2.0±1.35 mm, p<0.001; Area: +13.31±10.92 mm2, p<0.001 and Perimeter: +4.79±3.4 mm, p<0.001) and IVUS (Dmax: +1.52±2.16 mm, p<0.001; Area: +10.03±21.5 mm2, p<0.001 and Perimeter: +4.15±3.27 mm, p<0.001). The TOF-MRV sinus measurements were in good agreement with the IVUS measurements with no significant variation (Dmax: +.21±2.23 mm, p = 0.49; Area: +2.51±20.41mm2, p = 0.347 and Perimeter: +.001±1.11 mm, p = 0.991). CONCLUSION:We report baseline cerebral venous sinus measurements (maximum diameter, area and perimeter) in patients with idiopathic intracranial hypertension. In our experience, TOF-MRV is a reliable representation of endoluminal cerebral venous sinus dimensions, and CE-MRV measurements reflected an overestimation of the endoluminal sinus dimensions when compared against the real time IVUS measurements.

Project description:BackgroundOphthalmic outcomes following venous sinus stenting (VSS) in patients with idiopathic intracranial hypertension (IIH) are not well characterized.Materials and methodsA retrospective chart review was conducted on 86 consecutive patients with IIH who underwent venous sinus stenting at Mayo Clinic, Rochester, Minnesota and Stanford Medical Center, Palo Alto, California between May 2015 and October 2021. Patients with raised intracranial pressure from a non-IIH etiology were excluded. Clinical symptoms and neuro-ophthalmological data, including best corrected visual acuity (BCVA), visual field mean deviation, papilledema, and optical coherence tomography (OCT) peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell inner plexiform layer (GC-IPL), were analyzed. Baseline measurements before VSS and 3 months or more postoperatively were compared.ResultsEighty-six subjects (82 female) were included in this study, with a median age of 33 (16-68) years and a median body mass index of 36.69 (22.30-62.00) kg/m2. 85/86 (98.8%) had attempted prior management with medication, and 12/86 (14%) had prior surgical management with optic nerve sheath fenestration, ventriculoperitoneal shunt, or bariatric surgery. Prior to VSS, 67/86 (77.9%) had papilledema, 85/86 (98.8%) had headaches, and 68/86 (79.1%) had pulsatile tinnitus. For patients with both pre- and post-VSS data available, the average papilledema grade was 1.76 (0-5) (n = 74) and the average OCT pRNFL was 186.34 (52.00-588.00) µm (n = 70), prior to VSS. A median of 4.0 (interquartile range 3.3-5.4) months after VSS, the average papilledema grade improved to 0.39 (0-2), p <0.001, and OCT pRNFL improved to 96.86 (47.00-168.00) µm, p <0.001. 28/86 (32.6%) patients no longer required medication for high intracranial pressure. 14/85 (16.5%) patients reported complete resolution of their headache and 55/71 (77.5%) reported improvement in headache quality. 40/68 (66.7%) reported complete resolution of pulsatile tinnitus. OCT GC-IPL, BCVA, and visual field mean deviation did not significantly change pre- vs post-VSS.ConclusionsOur large consecutive case series corroborates smaller prior studies in demonstrating the overall efficacy of VSS for patients with IIH. We found both ophthalmic improvements, as demonstrated by the significantly reduced papilledema and pRNFL, and overall clinical symptom improvement.

Project description:PurposeTo evaluate the alteration of pressure characteristics in the cerebral venous sinuses before and after venous sinus stenting (VSS) using mean sinus pressures (MSPs), sinus pressure gradient (SPG), and sinus pressure pulsatility (SPP) parameters among the idiopathic intracranial hypertension (IIH) patients.Materials and methodsProspective evaluation of 45 consecutive IIH patients who underwent VSS at our institution. A written informed consent approved by the Weill Cornell Institutional Review Board was signed by the study participants. All patients (n = 45) were evaluated for MSPs and SPG. In a subgroup of 12 (n = 12) consecutive patients, SPP was measured. MSP was measured using microcatheter at superior sagittal sinus (SSS), transverse sinus (TS), and sigmoid sinus (SS). SPG was measured as trans-stenotic gradient and trans-torcular gradient. SPP was recorded in the dominant TS with a six French intermediate catheter. Statistical analysis was performed using paired student t-test and two sample t-tests tested for both equal and unequal variances. P values below 0.05 were considered significant.ResultsThe mean age of the study population was 30.6 ± 10 years (7-59 years) and 43 out of 45 are female patients. The mean weight and BMI of the study population were 96 ± 24.7 kg (30.8-144 kg) and 35.6 ± 8.3 kg/M2 (16.4-51.4 kg/M2), respectively. VSS in IIH patients resulted in immediate reduction of MSP in the SSS {Δ Mean: -8.1 mm Hg [95% confidence interval (CI): -5.0-11.7 mm Hg], p < 0.001} and TS [Δ Mean: -11.8 mm Hg (95% CI: -7.5 to 13.4 mm Hg), p < 0.001] and increase of MSP in SS [Δ Mean: 7.5 mm Hg (95% CI: 6-10.1 mm Hg), p < 0.001]. Significant reduction of trans-stenotic SPG reduction [Δ Mean: -15.7 mm Hg (95% CI: -13.6-17.8 mm Hg), p < 0.001] and SPP [Δ Mean: -8 mm Hg (95% CI: -2.5-13.4 mm Hg), p < 0.05] was observed following VSS.ConclusionVSS resulted in immediate alteration of the cerebral venous sinus pressure measurements in patients with IIH.

Dataset Information

Interplay between VEGF and Nrf2 regulates angiogenesis due to intracranial venous hypertension.

Publications

Interplay between VEGF and Nrf2 regulates angiogenesis due to intracranial venous hypertension.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets