Vascular Endothelial Growth Factor (VEGF) is a powerful signaling protein that triggers the formation of new blood vessels (vasculature). Its primary function is to ensure the health and survival of the endothelial cells that line these vessels. Maintaining appropriate VEGF levels is essential for the body’s ability to deliver oxygen and nutrients throughout its tissues and to heal from injury. When this protein drops below normal concentrations, the necessary infrastructure for tissue maintenance fails, leading to significant disruptions in physiological function and contributing to several chronic health issues.
The Role of Vascular Endothelial Growth Factor
VEGF is a member of a family of growth factors, with VEGF-A being the most studied for its role in stimulating blood vessel formation, a process known as angiogenesis. This protein acts as a mitogen, promoting the division and proliferation of endothelial cells, which are the building blocks of blood vessel walls. VEGF sustains the health of existing vasculature by preventing the programmed death of endothelial cells. It is essential for ensuring that every cell in the body receives an adequate supply of oxygen and glucose. The factor also plays a part in wound healing by rapidly promoting the growth of blood vessels into damaged tissue.
Physiological Consequences of Impaired Angiogenesis
A sustained reduction in VEGF causes vascular rarefaction, which is the loss or thinning of the microvascular network. This regression diminishes the circulatory system’s capacity to deliver blood to specific organs and tissues. Poor tissue perfusion results in chronic ischemia, where affected areas are deprived of sufficient oxygen and nutrients. This oxygen deprivation leads to substantial tissue damage, especially in organs with high metabolic demands, such as the nervous system.
Failure of the microvasculature also severely impairs the body’s ability to repair itself following damage. Low VEGF prevents the necessary vessels from forming to support the growth of new tissue, often leading to chronic non-healing ulcers. This systemic failure of vascular support is the core biological mechanism linking low VEGF to various clinical diseases.
Clinical Conditions Linked to Low VEGF
Low levels of circulating VEGF contribute to several serious clinical conditions, particularly those involving neurodegeneration and chronic tissue damage. Amyotrophic Lateral Sclerosis (ALS), a progressive motor neuron disease, is strongly associated with gene variations that result in lower VEGF plasma levels. This reduced signaling is thought to impair spinal cord perfusion, subjecting motor neurons to chronic ischemia and depriving them of the protein’s neuroprotective signals. Decreased serum VEGF concentrations are also observed in patients with Alzheimer’s Disease (AD), suggesting that the decline in vascular health may contribute to the neurodegenerative process in this condition.
In the respiratory system, decreased VEGF in the pulmonary arteries is associated with pulmonary emphysema. Chronic wounds, such as diabetic foot ulcers, often exhibit low local VEGF concentrations, which directly contributes to delayed closure and poor healing. Furthermore, insufficient blood vessel formation (hypo-angiogenesis) driven by reduced VEGF, is hypothesized to play a role in the pathogenesis of dry age-related macular degeneration (Dry AMD).
Measuring and Modulating VEGF Levels
VEGF levels are measured using laboratory techniques like the Enzyme-Linked Immunosorbent Assay (ELISA) on blood samples. Clinicians analyze either plasma or serum to determine concentrations, but the results differ. Plasma measurement reflects the free, circulating protein, while serum levels are higher because they include VEGF released from platelets during clotting. A single measurement provides only a snapshot, and interpretation must consider the patient’s clinical context and the possibility of localized tissue concentrations differing from those in the blood.
For individuals with documented low VEGF, therapeutic and lifestyle strategies focus on safely increasing its production. Moderate, consistent exercise is a well-established method known to naturally enhance VEGF generation and promote healthier blood vessel growth. Certain dietary components and supplements support the pathways involved in VEGF production:
- Resveratrol
- Curcumin
- Omega-3 fatty acids
- Zinc
- Vitamin D
In clinical settings, hyperbaric oxygen therapy has been explored for its potential to increase VEGF and enhance tissue repair. While past trials using recombinant VEGF-A showed limited benefit, research continues into targeted gene therapies and growth factor administration to selectively boost VEGF where it is needed most.