- Vascular Permeability Factor (VPF) is the original name given to what is now more commonly known as Vascular Endothelial Growth Factor-A (VEGF-A).
- It was first described in the 1980s, when researchers observed a protein secreted by tumor cells that caused a dramatic increase in vascular permeability, leading to plasma leakage into surrounding tissues. Later, it was discovered that VPF and VEGF-A were the same molecule, but the term VPF highlights one of VEGF-A’s most characteristic biological effects—its ability to enhance the permeability of blood vessels.
- As VPF/VEGF-A, the protein is secreted as a glycoprotein that acts primarily on endothelial cells, the cells lining blood vessels. It exerts its effects by binding to specific receptors on endothelial cells, mainly VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). While VEGFR-2 mediates most of the angiogenic and permeability effects, VEGFR-1 may function as a regulator by sequestering VEGF-A and fine-tuning its activity. When VPF binds to these receptors, it activates intracellular signaling pathways that increase endothelial cell permeability. This occurs through mechanisms such as disruption of tight junctions between endothelial cells, reorganization of the cytoskeleton, and induction of fenestrations (small pores) in the endothelial lining. The result is leakage of plasma proteins like fibrinogen, which deposit into tissues and form a provisional matrix that supports the migration of endothelial cells during angiogenesis.
- Physiologically, the vascular permeability-inducing action of VPF/VEGF-A is important in processes such as wound healing, tissue repair, and embryonic development. By allowing plasma proteins and nutrients to exit blood vessels, it facilitates the creation of an extracellular environment conducive to new vessel formation. However, excessive vascular permeability can be harmful. In tumors, for example, high levels of VPF/VEGF-A secreted by cancer cells cause persistent plasma leakage, leading to the formation of abnormal, leaky vessels that support tumor growth and metastasis. Similarly, in ocular diseases such as diabetic retinopathy and age-related macular degeneration, overproduction of VPF/VEGF-A causes leakage from fragile retinal vessels, resulting in edema and vision loss.
- Clinically, understanding VPF’s role in vascular permeability has been transformative. Anti-VEGF therapies, such as bevacizumab (a monoclonal antibody against VEGF-A) and ranibizumab (a fragment antibody used in eye diseases), are widely used to block VEGF-A/VPF activity. By inhibiting this pathway, these therapies reduce abnormal vessel leakage, edema, and neovascularization, improving outcomes in cancer and ophthalmology. On the other hand, controlled stimulation of VPF/VEGF-A activity has therapeutic potential in ischemic diseases, where increasing vessel permeability and angiogenesis could restore blood flow to oxygen-deprived tissues.
