Vascular Endothelial Growth Factor: Physiology and What Research Reports

What Vascular Endothelial Growth Factor Is

Vascular endothelial growth factor (VEGF) is a family of secreted signalling proteins whose main targets are endothelial cells — the cells that line blood and lymphatic vessels. Binding of VEGF to its receptors promotes endothelial cell survival, division, migration and vessel permeability, and is a required step in the formation of new vessels (angiogenesis). A broad review of the field described VEGF as a central regulator of both physiological and pathological vessel formation and traced its path from basic laboratory discovery to clinical application (PMID 30486258).

The human family includes VEGF-A, VEGF-B, VEGF-C, VEGF-D and placental growth factor. These ligands signal through receptor tyrosine kinases conventionally labelled VEGFR-1, VEGFR-2 and VEGFR-3, with VEGFR-2 most closely associated with blood vessel sprouting and VEGFR-3 with lymphatic biology. Soluble forms of the receptors circulate and can bind ligand without transmitting a signal, which is why some clinical studies measure ligand and soluble receptor together.

Where It Is Produced and What It Does in the Body

VEGF is not confined to one organ. It is expressed by many cell types, including vascular smooth muscle, macrophages, fibroblasts, epithelial cells and a wide range of tumour cells, and its transcription is strongly induced by low oxygen tension through hypoxia-inducible signalling. In broad terms, tissue that is hypoxic or healing raises local VEGF output, endothelial cells respond, and new capillaries grow toward the signal. The same review that summarised VEGF biology also emphasised that this single pathway underlies processes as different as embryonic vascular patterning, wound repair and tumour vascularisation (PMID 30486258).

Because vessel growth is tightly regulated, VEGF does not act alone. Investigators studying nasal polyp tissue examined VEGF alongside the endogenous anti-angiogenic factors angiostatin and endostatin, framing polyp development as a balance between pro- and anti-angiogenic signals rather than the action of one molecule (PMID 39665059).

How VEGF Is Measured and Studied

Several complementary approaches appear in the published literature:

• Circulating protein in blood. A 2022 study measured VEGF and its soluble receptor in patients with systemic lupus erythematosus, comparing levels with clinical features of the disease (PMID 36551311).
• Tissue immunostaining. A veterinary study reported reduced VEGF immunostaining in canine splenic hemangiosarcoma tissue in the context of thalidomide exposure (PMID 32443710).
• Receptor expression in lesions. Researchers compared vascular endothelial growth factor receptor expression in orbital cavernous malformations and lymphatic malformations, an approach that asks which receptor subtypes are present rather than how much ligand circulates (PMID 34308441).
• Cell-based angiogenesis assays. A 2020 laboratory study reported that the flavonoid fisetin inhibited VEGF-induced angiogenesis in retinoblastoma cells, using VEGF as the stimulus against which an inhibitor was tested (PMID 32724364).

What the Literature Reports

Blocking VEGF: the therapeutic side of the pathway

The most developed clinical application of VEGF biology is inhibition rather than supplementation. A review in Nature Reviews Drug Discovery surveyed ten years of anti-VEGF therapy, summarising how antibody-based and receptor-decoy agents moved from concept to routine use in neovascular eye disease and oncology, and what that decade of experience taught the field (PMID 26775688). In paediatric ophthalmology, an updated literature review examined anti-VEGF therapy for retinopathy of prematurity, collating reported outcomes and the open questions that remain in that population (PMID 36276253).

Oncology and treatment resistance

In metastatic colorectal cancer, a 2024 paper examined how features of the VEGF pathway influence the efficacy of the anti-VEGF antibody bevacizumab, a line of work aimed at explaining why the same agent performs differently across patients (PMID 39554750). Separately, researchers reviewed the role of VEGF in radiotherapy resistance in oesophageal squamous cell carcinoma, positioning the pathway as one mechanism by which tumours withstand radiation (PMID 35767192). Preclinical and veterinary work continues to use VEGF as a readout: the canine hemangiosarcoma study reported lower VEGF immunostaining in treated tissue (PMID 32443710), and the retinoblastoma cell study reported inhibition of VEGF-driven angiogenic behaviour (PMID 32724364).

Non-malignant tissue

VEGF also appears as a biomarker in inflammatory and structural conditions. The lupus study measured ligand and soluble receptor in patients to ask whether these markers tracked with disease activity (PMID 36551311), while the nasal polyp work treated the pro- versus anti-angiogenic balance as relevant to tissue remodelling (PMID 39665059).

Why VEGF Matters to Peptide and Protein Research

VEGF is a protein growth factor rather than a short synthetic peptide, but it is a standard teaching example in the same literature that peptide researchers read, for two reasons.

1. Stability and half-life engineering. A 2024 study in ACS Biomaterials Science & Engineering reported on PEGylation of human vascular endothelial growth factor, applying the same polyethylene glycol conjugation strategy used with many therapeutic peptides and proteins to alter the molecule's properties (PMID 37296497).
2. Localised delivery. A 2018 study loaded VEGF into microspheres and reported effects on dental pulp regeneration and vascularisation, illustrating why growth factors are often formulated for slow local release rather than delivered as free protein (PMID 29972963).

Readers encountering VEGF in a peptide or bioregulator context most often meet it as a mechanism claim — that some compound raises or lowers VEGF expression — rather than as a product. The cited literature shows why such claims require care: VEGF activity is context-dependent, and the same pathway that supports healing also supports tumour and neovascular disease (PMID 30486258).

Safety, Limits and Open Questions: What Studies Report

None of the papers listed here establish a safe or effective way for an individual to alter their own VEGF levels. The ten-year review of anti-VEGF therapy discussed both the clinical impact and the remaining challenges of targeting this pathway (PMID 26775688), and the retinopathy of prematurity review compiled reported efficacy and safety considerations rather than issuing a single recommendation (PMID 36276253). Biomarker studies such as the lupus cohort were observational and measured associations, not causation (PMID 36551311), while the fisetin and microsphere findings came from cell and preclinical models whose results do not transfer directly to people (PMID 32724364, PMID 29972963).

This page is for educational purposes only and is not medical advice; consult a licensed physician about any medical condition, medication or laboratory result.

References

• Vascular Endothelial Growth Factor, from Basic Research to Clinical Applications (International Journal of Molecular Sciences, 2018)
• Ten years of anti-vascular endothelial growth factor therapy (Nature Reviews Drug Discovery, 2016)
• Anti-vascular endothelial growth factor therapy in retinopathy of prematurity: An updated literature review (Saudi Journal of Ophthalmology, 2022)
• Vascular endothelial growth factor pathway's influence on bevacizumab efficacy in metastatic colorectal cancer treatment (World Journal of Gastrointestinal Oncology, 2024)
• Role of vascular endothelial growth factor in radiotherapy resistance to esophageal squamous cell carcinoma (Journal of Cancer Research and Clinical Oncology, 2023)
• Vascular Endothelial Growth Factor and Its Soluble Receptor in Systemic Lupus Erythematosus Patients (Biomolecules, 2022)
• The Roles of Vascular Endothelial Growth Factor, Angiostatin, and Endostatin in Nasal Polyp Development (Journal of Rhinology, 2022)
• Vascular Endothelial Growth Factor Receptor Expression in Orbital Cavernous Malformations and Lymphatic Malformations (Ophthalmology and Vision Care, 2021)
• Fisetin inhibits vascular endothelial growth factor-induced angiogenesis in retinoblastoma cells (Oncology Letters, 2020)
• Thalidomide Reduces Vascular Endothelial Growth Factor Immunostaining in Canine Splenic Hemangiosarcoma (Veterinary Sciences, 2020)
• PEGylation of Human Vascular Endothelial Growth Factor (ACS Biomaterials Science & Engineering, 2024)
• Vascular endothelial growth factor-loaded microspheres promote dental pulp regeneration and vascularization (Chinese Journal of Stomatology, 2018)