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The role of VEGF and KDR polymorphisms in moyamoya disease and collateral revascularization.

ABSTRACT: We conducted a case-control study to investigate whether vascular endothelial growth factor (VEGF -2578, -1154, -634, and 936) and kinase insert domain containing receptor (KDR -604, 1192, and 1719) polymorphisms are associated with moyamoya disease. Korean patients with moyamoya disease (n = 107, mean age, 20.9±15.9 years; 66.4% female) and 243 healthy control subjects (mean age, 23.0±16.1 years; 56.8% female) were included. The subjects were divided into pediatric and adult groups. Among the 64 surgical patients, we evaluated collateral vessel formation after 2 years and divided patients into good (collateral grade A) or poor (collateral grade B and C) groups. The frequencies and distributions of four VEGF (-2578, -1154, -634, and 936) and KDR (-604, 1192, and 1719) polymorphisms were assessed from patients with moyamoya disease and compared to the control group. No differences were observed in VEGF -2578, -1154, -634, and 936 or KDR -604, 1192, and 1719 polymorphisms between the control group and moyamoya disease group. However, we found the -634CC genotype occurred less frequently in the pediatric moyamoya group (p = 0.040) whereas the KDR -604C/1192A/1719T haplotype increased the risk of pediatric moyamoya (p = 0.024). Patients with the CC genotype of VEGF -634 had better collateral vessel formation after surgery. Our results suggest that the VEGF -634G allele is associated with pediatric moyamoya disease and poor collateral vessel formation.

SUBMITTER: Park YS

PROVIDER: S-EPMC3470587 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The role of VEGF and KDR polymorphisms in moyamoya disease and collateral revascularization.

Park Young Seok YS Jeon Young Joo YJ Kim Hyun Seok HS Chae Kyu Young KY Oh Seung-Hun SH Han In Bo IB Kim Hyun Sook HS Kim Won-Chan WC Kim Ok-Joon OJ Kim Tae Gon TG Choi Joong-Uhn JU Kim Dong-Seok DS Kim Nam Keun NK

PloS one 20121012 10

We conducted a case-control study to investigate whether vascular endothelial growth factor (VEGF -2578, -1154, -634, and 936) and kinase insert domain containing receptor (KDR -604, 1192, and 1719) polymorphisms are associated with moyamoya disease. Korean patients with moyamoya disease (n = 107, mean age, 20.9±15.9 years; 66.4% female) and 243 healthy control subjects (mean age, 23.0±16.1 years; 56.8% female) were included. The subjects were divided into pediatric and adult groups. Among the 6 ...[more]

PMID: 23077562

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Project description:Objective: To evaluate clinical and radiological outcomes after revascularization of hemorrhagic moyamoya disease (MMD). Materials and Methods: We retrospectively collected patients with hemorrhagic MMD who received revascularization from January 2011 to June 2018 at a high-volume stroke center. Rebleeding, ischemic stroke, modified Rankin Scale (mRS) and death after revascularization were used to evaluate long-term clinical outcome. Poor neurological outcome was defined as a mRS>2. The changes of original and revascularization collaterals were used to evaluate radiological outcome. The clinical and radiological outcomes between patients with different surgical revascularization were compared. Results: A total of 312 patients (319 hemispheres) were recruited, including 133 hemispheres (41.7%) with indirect revascularization and 186 hemispheres (58.3%) with direct revascularization. In 308 hemispheres with clinical follow-up data, Postoperative rebleeding, ischemic stroke, poor neurological outcome and death occurred in 13.0% (40/308), 2.6% (8/308), 12.0% (37/308), and 6.2% (19/308) of the hemispheres, respectively. The rates of postoperative rebleeding (8.5 vs. 19.1%, P = 0.006) and poor neurological outcome (8.5 vs. 16.8%, P = 0.026) were lower in hemispheres with direct revascularization than those with indirect revascularization. However, there was no statistically significant difference in the rates of postoperative ischemic stroke (1.1 vs. 4.6%, P = 0.129) and death (4.5 vs. 8.4%, P = 0.162) between the two groups. Multivariate logistic regression analysis indicated that the risk of postoperative rebleeding was higher in those with untreated aneurysms, repetitive bleeding episodes, normal perfusion status, and indirect revascularization (P < 0.05). In 78 hemispheres with radiological follow-up data, the regression of moyamoya vessels, anterior choroidal artery (AchA), posterior communicating artery (PcomA) and aneurysms were present in 44.9, 47.4, 25.6, and 11.5% of the hemispheres, respectively. The regression of original collaterals and establishment of revascularization collaterals were more significant in hemispheres with direct revascularization than those with indirect revascularization (P < 0.05). Conclusion: Direct revascularization may be superior to indirect revascularization for prevention of rebleeding and poor neurological outcome in adults with hemorrhagic MMD. The risk of postoperative rebleeding was higher in those with untreated aneurysms, repetitive bleeding episodes, normal perfusion status, and indirect revascularization. The regression of original collaterals and establishment of revascularization collaterals after revascularization were more significant in hemispheres with direct revascularization than those with indirect revascularization.

Project description:ObjectiveMoyamoya disease (MMD) is a unique cerebrovascular occlusive disease characterized by progressive steno-occlusion within the terminal segment of the internal carotid artery. However, good collaterals from an external carotid artery are essential to compensate for the ischemia in moyamoya disease. This study aimed to investigate the transforming growth factor-beta 1 (TGFβ1) in plasma as a potential biomarker for predicting collateral formation in ischemic MMD.MethodsThe transcriptome profile downloaded from Gene Expression Omnibus (GEO) was used to analyze the differential expression of genes between the ischemic MMD and the control groups. We prospectively recruited 23 consecutive patients with ischemic MMD that was diagnosed via digital subtraction angiography (DSA). Nine patients with intracranial aneurysms and four healthy people served as controls. The collaterals from the external carotid artery were examined using DSA. We evaluated whether the collateral formation was associated with TGFβ1 in patients with ischemic MMD. Western blot, RT-qPCR, ELISA, and tube formation assay were used to explore the relationship between TGFβ1 and angiogenesis, as well as the potential mechanisms.ResultsThe mRNA levels of TGFβ1 were upregulated in the patients with ischemic MMD. The plasma TGFβ1 levels were higher in the patients with ischemic MMD than in the aneurysm and healthy patients (p < 0.05). The collateral formation group has higher levels of serum TGFβ1 than the non-collateral formation group (p < 0.05). The levels of vascular endothelial growth factor (VEGF) are positively correlated with TGFβ1 levels in the plasma (R 2 = 0.6115; p < 0.0001). TGFβ1 regulates VEGF expression via the activation of the TGFβ pathway within HUVEC cells, as well as TGFβ1 stimulating HUVEC cells to secrete VEGF into the cell culture media. An in vitro assay revealed that TGFβ1 promotes angiogenesis within the endothelial cells.ConclusionOur findings suggest that TGFβ1 plays a vital role in promoting collateral formation by upregulating VEGF expression in ischemic MMD.

Project description:AimPrevious studies have found significant differences in clinical characteristics between pediatric and adult moyamoya disease (MMD) patients, but few studies have focused on the factors underlying these differences. We aimed to investigate the differences in leptomeningeal collateral (LMC) status between pediatric and adult MMD patients and to analyze the effects of LMCs on clinical characteristics and therapeutic prognosis.MethodsWe retrospectively analyzed 214 MMD patients from January 2014 to January 2016. Clinical characteristics and LMC status were compared between the pediatric and adult patients. LMC status was graded as good or poor depending on the retrograde flow from the posterior cerebral artery (PCA) on digital subtraction angiography (DSA).ResultsA total of 83 pediatric and 131 adult (1:1.6) MMD patients were analyzed. Pediatric patients were more likely to experience a transient ischemic attack (81%), whereas adult patients were more likely to experience infarction (51%). Regarding the different MMD stages (the early, medium, and advanced stages corresponded to Suzuki stages 1-2, 3-4, and 5-6, respectively), the prevalence of good LMC status was higher for pediatric patients than for adult patients in the early stage (P = 0.047) and the medium stage (P = 0.001), but there were no differences between these patient groups in the advanced stage (P = 0.547). Worse postoperative angiographic outcomes (P = 0.017) were found in adult patients than in pediatric patients in the medium stage. Poor LMC status had strong correlations with infarction (P < 0.001 and P = 0.017) and poor postoperative outcomes (P = 0.003 and P = 0.043) in both pediatric and adult patients.ConclusionsPediatric MMD patients have greater patency and a greater ability to establish good LMC status than adult patients, and poor LMC status has a strong correlation with severe clinical symptoms and poor postoperative outcomes. LMC status may be an important factor in the differences in clinical characteristics and prognosis between pediatric and adult MMD patients.

Dataset Information

The role of VEGF and KDR polymorphisms in moyamoya disease and collateral revascularization.

Publications

The role of VEGF and KDR polymorphisms in moyamoya disease and collateral revascularization.

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