Vascular Endothelial Growth Factor (VEGF) is a complex signaling protein naturally found in the body, playing an important role in various biological processes. It contributes to both normal bodily functions and the progression of certain diseases. Understanding VEGF’s activity provides insight into how the body regulates its systems and how disruptions can lead to health challenges.
What is Vascular Endothelial Growth Factor?
Vascular Endothelial Growth Factor (VEGF) is a protein that promotes the formation of new blood vessels. This process, termed angiogenesis, involves the growth of new capillaries from existing ones. VEGF-A is a key stimulator of both vasculogenesis, the initial formation of the circulatory system, and angiogenesis.
VEGF initiates its effects by binding to specific receptors on endothelial cells, which line blood vessels. These receptors include VEGFR1, VEGFR2, and VEGFR3. This binding stimulates endothelial cells to grow, multiply, and migrate, leading to new blood vessel formation. VEGF-A also increases vascular permeability, allowing fluids and proteins to leak from blood vessels.
How VEGF Supports Normal Body Functions
In a healthy body, VEGF performs several beneficial and necessary roles, with its activity tightly controlled. During embryonic development, for instance, VEGF is essential for the initial formation of the circulatory system. This early stage ensures the developing organism receives adequate blood supply to support its growth.
VEGF also plays a role in wound healing, aiding tissue repair. Following an injury, cells like platelets and macrophages release VEGF into the wound site. This promotes the growth of new blood vessels, which deliver oxygen and nutrients to the healing area. VEGF also promotes the migration of keratinocytes, cells involved in skin repair, and stimulates collagen production, a structural protein crucial for tissue strength. Its expression is also upregulated during physiological processes like menstruation and ovulation.
VEGF’s Role in Illness
When VEGF regulation is disrupted, through excessive production or insufficient activity, it can contribute to the development and progression of various diseases. In many cancers, tumors exploit VEGF to establish their own blood supply. This abnormal blood vessel growth, called tumor angiogenesis, provides the tumor with the oxygen and nutrients it needs to grow and survive.
These new, often leaky, vessels also serve as pathways for cancer cells to spread to other parts of the body, a process known as metastasis. High levels of VEGF-A are often observed in cancers, correlating with increased tumor angiogenesis and reduced survival rates. Uncontrolled VEGF activity thus contributes significantly to cancer progression.
Excessive VEGF activity is also implicated in several serious eye conditions that can lead to vision loss. In wet Age-related Macular Degeneration (AMD), abnormal and fragile blood vessels grow underneath the retina, specifically in the choroid. These vessels often leak fluid and blood, which damages the macula, the part of the retina responsible for sharp, central vision. VEGF contributes to this pathological vessel growth.
Similarly, in diabetic retinopathy, persistently high blood sugar levels can damage retinal blood vessels, leading to poor blood flow. In response to this oxygen deprivation, the retina produces excessive VEGF, triggering the growth of new, weak blood vessels. These new vessels are prone to bleeding and leakage, causing complications like diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR), both of which severely impair vision. VEGF also disrupts the blood-retinal barrier in these conditions.
Targeting VEGF in Medical Treatments
Understanding VEGF’s involvement in disease has led to the development of targeted medical therapies. These “anti-VEGF” treatments block the activity of VEGF or its receptors, interfering with the abnormal blood vessel formation and leakage that characterize many illnesses.
In cancer treatment, anti-VEGF drugs inhibit the growth of new blood vessels that tumors rely on, essentially “starving” the tumor by cutting off its nutrient and oxygen supply. These therapies can slow tumor progression and are often used with chemotherapy. Approved drugs for various cancers include bevacizumab, sunitinib, and sorafenib.
For eye diseases like wet AMD and diabetic retinopathy, anti-VEGF medications are administered directly into the eye via injections. This localized approach effectively stops the growth and leakage of abnormal blood vessels, helping to preserve or improve vision. Common anti-VEGF drugs used in ophthalmology include ranibizumab, aflibercept, bevacizumab, brolucizumab, and faricimab. While generally safe, the primary risk is a rare possibility of infection.