VEGF

Background

Vascular Endothelial Growth Factor A (VEGF-A or VEGF) is a vital VEGF/PDGF growth factor family member. It typically exists as several isoforms due to alternative splicing, notably VEGF-A121, VEGF-A165, and VEGF-A189, differing in their ability to bind to extracellular matrix components. Various cell types, including endothelial cells, macrophages, and some tumor cells, primarily produce VEGF-A. Its primary function involves promoting angiogenesis, which is crucial for embryonic development. VEGF-A governs critical aspects of endothelial cell (EC) responses, including EC proliferation, migration, vascular permeability, and the differentiation between tip and stalk cells. VEGF-A also regulates organ homeostasis in adults and increases the organ's regeneration rate.

Its Gene ID: 7422, UniProtKB ID: P15692, and OMIM ID: 192240.

VEGF-A Receptors

Hypoxia and various growth factors stimulate VEGF-A production. It binds primarily to VEGFR1 and VEGFR2 on cell surfaces, triggering VEGFR2 autophosphorylation and activating downstream signaling pathways that promote endothelial cell proliferation and migration. VEGFR1 also exhibits tyrosine kinase activity but primarily acts as a decoy receptor to modulate VEGF-A bioavailability and enhance VEGFR2 signaling.

VEGFR2-Dependent Signaling Pathways

Several signaling pathways are activated upon VEGF-A binding to VEGFR2 to regulate endothelial cell functions crucial for angiogenesis. VRAP and Nck signaling play vital roles in restructuring the cell's structural components, enabling cells to migrate to where they are required. VEGFR2 triggers phosphorylation cascades that activate VRAP, facilitating endothelial cell migration and permeability, and Nck adaptor proteins link VEGFR2 to cytoskeletal remodeling via actin dynamics. PLC-γ activation leads to intracellular calcium release, influencing cell proliferation and migration. Src kinases promote endothelial cell survival and proliferation through various downstream effectors. FAK activation enhances cell migration and survival by modulating focal adhesion turnover. The PI3K-Akt pathway promotes cell survival and endothelial nitric oxide synthase (eNOS) activation, regulating vascular tone and permeability. These pathways regulate vascular growth and maintenance, highlighting VEGFR2's central role in angiogenesis and vascular function in physiological and pathological contexts.

Fig. 1 The VEGF-A/VEGFR2 signaling pathway.^1,4

Role of VEGF-A in Tumor Progression and Other Diseases

VEGF-A plays a pivotal role in tumor progression by promoting angiogenesis, a critical tumor growth and metastasis process. Overexpression of VEGF-A is common in malignant tumors, stimulating endothelial cell proliferation and migration. This causes the creation of new blood vessels, which offer oxygen and nutrients to the cancer, facilitating its growth and progression. Additionally, VEGF-A enhances vascular permeability, aiding tumor cell intravasation and dissemination. Targeting VEGF-A signaling pathways has become a significant therapeutic strategy in cancer treatment, aiming to inhibit tumor angiogenesis and reduce tumor burden.

In POEMS syndrome, VEGF-A levels are elevated, contributing to the disease pathogenesis. The mechanism involves VEGF-A-mediated vascular endothelial growth and dysfunction, which manifests as polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. Elevated VEGF-A levels correlate with disease severity and progression in POEMS syndrome. In age-related macular degeneration (AMD) and diabetic retinopathy, VEGF-A overexpression leads to pathological angiogenesis in the retina. This results in retinal vascular leakage, edema, and neovascularization, resulting in vision loss. Anti-VEGF therapies have revolutionized the management of these conditions by reducing vascular permeability and preventing abnormal blood vessel growth.

Fig. 2 VEGF-A in endothelial cells and breast cancer stem cells promotes breast cancer progression.^2,4

VEGF Aptamer Analysis

Creative Biolabs provides a wide range of VEGF related products, including anti-VEGF aptamer. Our products can effectively help you conduct experiments and play an important role in your research.

Fig 3. The preparation of electrochemical sensor with VEGF₁₆₅ aptamer.^3,4

VEGF has been found to be a biomarker for angiogenesis in a variety of malignant tumors. Highly sensitive detection of this tumor marker is beneficial for rapid diagnosis and treatment of patients. VEGF₁₆₅ is a type of VEGF. When metastasis occurs, the abnormally rapid growth and division of the tumor can promote the overexpression of VEGF₁₆₅. High levels of VEGF₁₆₅ can be regarded as a predictor of different cancers, including lung, breast, brain, lymphoma, and gastrointestinal tumors. Therefore, VEGF₁₆₅ has been identified as a potential biomarker for the diagnosis of cancer. Yunjeong Park et al. designed an electrochemical aptamer sensor composed of a nanocomposite of polyaniline (PANI) and carbon nanotubes (CNTs) and a VEGF₁₆₅ aptamer.^3,4 This sensor can accurately detect VEGF₁₆₅ in human serum in the presence of interfering molecules such as HSA.

Creative Biolabs provides several aptamers targeting VEGF/VEGF-A that ensure reliable detection and precise analysis to accelerate your scientific research.

References

1. Kong, Meng, et al. "Infantile hemangioma models: is the needle in a haystack?." Journal of translational medicine 21.1 (2023): 308.
2. Zhu, Xiaoxia, and Wen Zhou. "The emerging regulation of VEGFR-2 in triple-negative breast cancer." Frontiers in endocrinology 6 (2015): 159.
3. Park, Yunjeong, et al. "Highly sensitive electrochemical aptasensor for detecting the VEGF₁₆₅ tumor marker with PANI/CNT nanocomposites." Biosensors 11.4 (2021): 114.
4. Distributed under Open Access license CC BY 4.0, without modification.