Association between VEGF-A and VEGFR-2 polymorphisms and response to treatment of neovascular AMD with anti-VEGF agents: a meta-analysis

Wu, Mingxing; Xiong, Haibo; Xu, Yan; Xiong, Xiaojing; Zou, Hongmi; Zheng, Mei; Wang, Xiuqing; Zhou, Xiyuan

doi:10.1136/bjophthalmol-2016-309418

Cited by 30 publications

(15 citation statements)

References 31 publications

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“…VEGFR family members include KDR (kinase insert domain-containing receptor; VEGFR-2), FLT1 (Fms-like tyrosine kinase; VEGFR-1), and FLT4 (VEGFR-3) (51). VEGFR-2 binds VEGF-A, which is expressed in vascular endothelial cells and hematopoietic stem cells (53). In the present study, we focused on VEGFR-2 and its downstream signaling in kaempferol-treated HUVECs.…”

Section: Discussionmentioning

confidence: 96%

Kaempferol inhibits angiogenic ability by targeting VEGF receptor-2 and downregulating the PI3K/AKT, MEK and ERK pathways in VEGF-stimulated human umbilical vein endothelial cells

et al. 2018

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Anti-angiogenesis is one of the most general clinical obstacles in cancer chemotherapy. Kaempferol is a flavonoid phytochemical found in many fruits and vegetables. Our previous study revealed that kaempferol triggered apoptosis in human umbilical vein endothelial cells (HUVECs) by ROS‑mediated p53/ATM/death receptor signaling. However, the anti‑angiogenic potential of kaempferol remains unclear and its underlying mechanism warranted further exploration in VEGF‑stimulated HUVECs. In the present study, kaempferol significantly reduced VEGF‑stimulated HUVEC viability. Kaempferol treatment also inhibited cell migration, invasion, and tube formation in VEGF‑stimulated HUVECs. VEGF receptor‑2 (VEGFR‑2), and its downstream signaling cascades (such as AKT, mTOR and MEK1/2‑ERK1/2) were reduced as determined by western blotting and kinase activity assay in VEGF‑stimulated HUVECs after treatment with kaempferol. The present study revealed that kaempferol may possess angiogenic inhibition through regulation of VEGF/VEGFR‑2 and its downstream signaling cascades (PI3K/AKT, MEK and ERK) in VEGF-stimulated endothelial cells.

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Section: Discussionmentioning

confidence: 96%

Kaempferol inhibits angiogenic ability by targeting VEGF receptor-2 and downregulating the PI3K/AKT, MEK and ERK pathways in VEGF-stimulated human umbilical vein endothelial cells

et al. 2018

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“…Other researchers are looking for associations between AMD risk alleles and response to anti-angiogenic treatment; one of the studies showed that anti-VEGF treatment was much more effective in patients with nAMD having rs833061 (CC versus TT: OR=2.222, 95% CI 1.252; 3.944, p =0.006; CT versus TT: OR=2.537, 95% CI 1.478; 4.356, p =0.001 and CC versus CT+TT: OR=2.362, 95% CI 1.414; 3.946, p =0.001), [ 69 ]. In addition, newer technologies allow researchers to consider other insights into iPSC-RPE AMD modelling, by adding or eliminating the risk alleles for better response to the treatment [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

The Association Between Variants of Receptor for Advanced Glycation End Products (RAGE) Gene Polymorphisms and Age-Related Macular Degeneration

et al. 2018

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BackgroundAge-related macular degeneration (AMD) is the leading cause of blindness in people aged 65 years and older in developed countries. The pathogenesis of AMD has been linked to mechanisms involving inflammation, oxidative stress, and basal laminar deposit formation between retinal pigment epithelium (RPE) cells and the basal membrane, caused by advanced glycation end products (AGEs). AGEs are implicated in the pathogenesis of AMD through the AGE-and receptor for AGE (RAGE) interaction, which can be altered by polymorphisms of the RAGE gene. We examined RAGE rs1800624 and rs1800625 gene polymorphisms contributing to AMD development.Material/MethodsThe study enrolled 300 patients with early AMD, 300 patients with exudative AMD, and 800 healthy controls. The genotyping was carried out using the RT-PCR method.ResultsThe analysis of two single nucleotide polymorphisms (SNPs) in the RAGE gene showed that rs1800624 was associated with a 1.6-fold decreased risk for exudative AMD under the dominant model after adjustment for age (OR=0.616; 95% CI: 0.394–0.963; p=0.034) and each copy of allele T at rs1800624 was associated with a 1.4-fold decreased risk for exudative AMD development under the additive model after adjustment for age (OR=0.701; 95% CI: 0.510–0.962; p=0.028). Analysis revealed that the rs1800625 allele G at rs1800625 was associated with a 1.5-fold increased risk for exudative AMD after adjustment for age (OR=1.545; 95% CI: 1.003–2.379; p=0.048). These results suggested that the allele G at rs1800625 was a risk-allele for exudative AMD development. In haplotype analysis, A-G haplotype was significantly more frequently observed in exudative AMD patients compared to healthy controls (3.3% versus 1.4%, p=0.035).ConclusionsWe revealed a significant association between RAGE gene rs1800624 and rs1800625 polymorphisms and AMD risk. We considered T allele at rs1800624 to be protective against AMD development, while allele G at rs1800625 was considered to be a marker of poor prognosis in AMD development.

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“…After evaluation of nine SNPs (rs699947, rs699946, rs833069, rs833061, rs2146323, rs1413711, rs2010963 and rs1570360 in VEGFA , and rs2071559 in KDR ), anti-VEGF treatment was found to be more effective in patients homozygous for the VEGFA rs833061 minor allele C, compared to the remaining AMD patients (OR = 2.362, 95% CI 1.41–3.95, P = 0.001). This analysis was, however, limited in sample size, including only 444 AMD patients from three independent studies [ 90 ]. An SNP (rs2070296) in the neuropilin-1 ( NRP1 ) gene, encoding the co-receptor for VEGF, has been associated with worse response to treatment in one study [ 91 ], but this SNP has not yet been evaluated in independent cohorts.…”

Section: Current Therapeutic Interventions For Age-related Macular Dementioning

confidence: 99%

Exploring the Use of Molecular Biomarkers for Precision Medicine in Age-Related Macular Degeneration

Lorés‐Motta¹,

Hollander

2018

Mol Diagn Ther

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Precision medicine aims to improve patient care by adjusting medication to each patient’s individual needs. Age-related macular degeneration (AMD) is a heterogeneous eye disease in which several pathways are involved, and the risk factors driving the disease differ per patient. As a consequence, precision medicine holds promise for improved management of this disease, which is nowadays a main cause of vision loss in the elderly. In this review, we provide an overview of the studies that have evaluated the use of molecular biomarkers to predict response to treatment in AMD. We predominantly focus on genetic biomarkers, but also include studies that examined circulating or eye fluid biomarkers in treatment response. This involves studies on treatment response to dietary supplements, response to anti-vascular endothelial growth factor, and response to complement inhibitors. In addition, we highlight promising new therapies that have been or are currently being tested in clinical trials and discuss the molecular studies that can help identify the most suitable patients for these upcoming therapeutic approaches.

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Association between VEGF-A and VEGFR-2 polymorphisms and response to treatment of neovascular AMD with anti-VEGF agents: a meta-analysis

Cited by 30 publications

References 31 publications

Kaempferol inhibits angiogenic ability by targeting VEGF receptor-2 and downregulating the PI3K/AKT, MEK and ERK pathways in VEGF-stimulated human umbilical vein endothelial cells

Kaempferol inhibits angiogenic ability by targeting VEGF receptor-2 and downregulating the PI3K/AKT, MEK and ERK pathways in VEGF-stimulated human umbilical vein endothelial cells

The Association Between Variants of Receptor for Advanced Glycation End Products (RAGE) Gene Polymorphisms and Age-Related Macular Degeneration

Exploring the Use of Molecular Biomarkers for Precision Medicine in Age-Related Macular Degeneration

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