Dataset Information

Differential Expression of Vascular Endothelial Growth Factor-A165 Isoforms Between Intracranial Atherosclerosis and Moyamoya Disease.

ABSTRACT: BACKGROUND:Vascular endothelial growth factor-A165 (VEGF-A165) has been identified as a combination of 2 alternative splice variants: proangiogenic VEGF-A165a and antiangiogenic VEGF-A165b. Intracranial atherosclerotic disease (ICAD) and moyamoya disease (MMD) are 2 main types of intracranial arterial steno-occlusive disorders with distinct capacities for collateral formation. Recent studies indicate that VEGF-A165 regulates collateral growth in ischemia. Therefore, we investigated if there is a distinctive composition of VEGF-A165 isoforms in ICAD and MMD. METHODS:Sixty-six ICAD patients, 6 MMD patients, and 5 controls were enrolled in this prospective study. ICAD and MMD patients received intensive medical management upon enrollment. Surgery was offered to 9 ICAD patients who had recurrent ischemic events, 6 MMD patients, and 5 surgical controls without ICAD. VEGF-A165a and VEGF-A165b plasma levels were measured at baseline, within 1 week after patients having surgery, and at 1, 3, and 6 months after treatment. RESULTS:A significantly higher baseline VEGF-A165a/b ratio was observed in MMD compared to ICAD (P?=?.016). The VEGF-A165a/b ratio increased significantly and rapidly after surgical treatment in ICAD (P?=?.026) more so than in MMD and surgical controls. In patients with ICAD receiving intensive medical management, there was also an elevation of the VEGF-A165a/b ratio, but at a slower rate, reaching the peak at 3 months after initiation of treatment (baseline versus 3 months VEGF-A165a/b ratio, P?=?.028). CONCLUSIONS:Our study shows an increased VEGF-A165a/b ratio in MMD compared to ICAD, and suggests that both intensive medical management and surgical revascularization elevate the VEGF-A165a/b ratio in ICAD patients.

SUBMITTER: Jiang H

PROVIDER: S-EPMC6786492 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Differential Expression of Vascular Endothelial Growth Factor-A165 Isoforms Between Intracranial Atherosclerosis and Moyamoya Disease.

Jiang Hao H Toscano Juan F JF Schiraldi Michael M Song Shlee S SS Schlick Konrad H KH Dumitrascu Oana M OM Liou Raymond R Lyden Patrick D PD Pan Jianwei J Zhan Renya R Saver Jeffrey L JL Gonzalez Nestor R NR

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 20181102 2

<h4>Background</h4>Vascular endothelial growth factor-A165 (VEGF-A165) has been identified as a combination of 2 alternative splice variants: proangiogenic VEGF-A165a and antiangiogenic VEGF-A165b. Intracranial atherosclerotic disease (ICAD) and moyamoya disease (MMD) are 2 main types of intracranial arterial steno-occlusive disorders with distinct capacities for collateral formation. Recent studies indicate that VEGF-A165 regulates collater ...[more]

PMID: 30392834

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Project description:PURPOSE:To assess systemic vascular endothelial growth factor (VEGF)-A levels after treatment with intravitreous aflibercept, bevacizumab, or ranibizumab. DESIGN:Comparative-effectiveness trial with participants randomly assigned to 2 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab after a re-treatment algorithm. PARTICIPANTS:Participants with available plasma samples (N = 436). METHODS:Plasma samples were collected before injections at baseline and 4-week, 52-week, and 104-week visits. In a preplanned secondary analysis, systemic-free VEGF levels from an enzyme-linked immunosorbent assay were compared across anti-VEGF agents and correlated with systemic side effects. MAIN OUTCOME MEASURES:Changes in the natural log (ln) of plasma VEGF levels. RESULTS:Baseline free VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were -0.30±0.61 pg/ml, -0.31±0.54 pg/ml, and -0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted confidence interval [CI]; P value) were -0.01 (-0.12 to +0.10; P = 0.89), -0.31 (-0.44 to -0.18; P < 0.001), and -0.30 (-0.43 to -0.18; P < 0.001) for aflibercept-bevacizumab, aflibercept-ranibizumab, and bevacizumab-ranibizumab, respectively. At 52 weeks, a difference in mean VEGF changes between bevacizumab and ranibizumab persisted (-0.23 [-0.38 to -0.09]; P < 0.001); the difference between aflibercept and ranibizumab was -0.12 (P = 0.07) and between aflibercept and bevacizumab was +0.11 (P = 0.07). Treatment group differences at 2 years were similar to 1 year. No apparent treatment differences were detected at 52 or 104 weeks in the cohort of participants not receiving injections within 1 or 2 months before plasma collection. Participants with (N = 9) and without (N = 251) a heart attack or stroke had VEGF levels that appeared similar. CONCLUSIONS:These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.

Dataset Information

Differential Expression of Vascular Endothelial Growth Factor-A165 Isoforms Between Intracranial Atherosclerosis and Moyamoya Disease.

Publications

Differential Expression of Vascular Endothelial Growth Factor-A<sub>165</sub> Isoforms Between Intracranial Atherosclerosis and Moyamoya Disease.

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