Vascular permeability is regulated by the endothelium and determines which molecules can pass through blood vessels. VEGF is the major determinant and is linked to cancer, but inhibiting it could prevent the spread of malignant tumors. Animal studies have shown some control of permeability in colon, brain, and breast cancer. Vascular permeability studies have also aided in the development of drugs that can cross the blood brain barrier to treat disease. The application of heat could increase vascular permeability at tumor sites.
Vascular permeability defines the ability of molecules to pass through blood vessels and reach tissues. A thin layer of cells that make up the vessels, called the endothelium, regulates the size of gas, nutrient and water molecules that can permeate the tissues. For example, the permeability of oxygen and carbon dioxide molecules allows for easy passage through the endothelium. Larger molecules, such as water and water-soluble substances, cannot permeate blood vessel walls. These molecules rely on tiny pores within the narrow joints of blood vessels to reach the tissues.
Several factors determine molecular permeability, which involves complex interactions of chemicals in the human body. Scientists discovered a peptide identified as vascular endothelial growth factor (VEGF) as the major determinant of vascular permeability. It works via dopamine, a neurotransmitter in the brain, to block or allow molecules from sticking to blood vessel walls.
VEGF is linked to cancer because it may stimulate cell receptors and increase the vascular permeability of cancer cells into tissue and bloodstream. Scientists believe that inhibiting this peptide could prevent the spread of malignant tumors through the blood. It could also prevent fluid from building up around the heart, where dopamine also regulates the permeability of fluid in the arteries.
Animal studies using certain antibodies show some control of permeability in colon, brain and breast cancer. These tests used dyes and magnetic resonance imaging (MRI) to measure the number of cancer cells that have crossed the blood brain barrier. Researchers have had some success in altering the movement of cancer cells through blood vessel walls.
Vascular permeability studies have also aided in the development of drugs that can cross the blood brain barrier to treat disease. Scientists initially found that disrupting this barrier opened the way for other toxins to enter the bloodstream. This has led to the discovery of chemotherapy agents that can selectively cross the barrier only where a tumor exists.
The application of heat could increase vascular permeability at tumor sites. Hyperthermia widens the size of pores within the blood vessels that feed tumors, which could allow heat-sensitive drugs to enter the tumor. Along with cancer, the drugs’ increased vascular permeability could be effective for treating diabetes, arthritis and heart disease.
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