Antiangiogenic substances inhibit the formation of new blood vessels. This inhibition has implications for biological functions and disease progression. Understanding their interaction with the vascular system offers insights into therapeutic strategies.
Understanding Angiogenesis
Angiogenesis is a biological process where new blood vessels form from existing ones. This process is different from vasculogenesis, which is the initial formation of endothelial cells during embryonic development. It continues the growth of the vascular network, primarily through sprouting and splitting.
In healthy individuals, angiogenesis is a regulated process for several bodily functions. It plays a role in growth and development, wound healing, and tissue repair, providing oxygen and nutrients to damaged areas. During embryogenesis, it establishes the initial vascular network, and in adults, it is involved in the menstrual cycle and tissue repair.
However, when angiogenesis becomes dysregulated, it can contribute to the progression of various diseases. A primary example is cancer, where tumors induce blood vessel growth to secure nutrients and oxygen, supporting their expansion and spread. This abnormal vessel formation is a hallmark of cancer, enabling rapid tumor growth and metastasis.
Pathological angiogenesis also contributes to conditions beyond cancer, including certain cardiovascular diseases like atherosclerosis and inflammatory disorders such as rheumatoid arthritis. In such cases, the uncontrolled growth of blood vessels can perpetuate inflammation or contribute to tissue damage. Controlling this process is important for managing these diseases.
How Antiangiogenic Approaches Work
Antiangiogenic approaches disrupt pathways that stimulate new blood vessel formation. They interfere with different stages of the angiogenic process, effectively “starving” unwanted growths of their blood supply. The goal is to prevent or slow the growth of new vessels rather than directly targeting diseased cells.
One common strategy involves blocking growth factors, such as vascular endothelial growth factor (VEGF), which are signals that promote angiogenesis. Some antiangiogenic agents are monoclonal antibodies that bind to VEGF, preventing it from activating its receptors on endothelial cells. This action stops the signals that would otherwise prompt new vessel growth.
Other antiangiogenic drugs inhibit the activation of VEGF receptors within endothelial cells. These are tyrosine kinase inhibitors (TKIs), blocking internal signaling pathways that lead to vessel formation. By targeting these mechanisms, TKIs can interfere with pro-angiogenic signals, including those from platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF).
Some therapies disrupt the communication between cells that promote angiogenesis, such as certain immunomodulatory drugs. These agents can interfere with chemical signals that orchestrate blood vessel development. While antiangiogenic agents do not directly kill cancer cells, they are often administered over extended periods, sometimes with other treatments, to slow or stop tumor progression by limiting nutrient supply.
Medical Applications
Antiangiogenic therapies have transformed treatment for several diseases, particularly cancer. In oncology, the idea is to inhibit the blood supply to tumors, restricting their access to oxygen and nutrients necessary for growth and metastasis. By preventing new blood vessels from forming, these therapies can slow tumor expansion or, in some cases, cause tumors to shrink.
Many antiangiogenic agents have received approval for treating various cancers, including colorectal, lung, breast, kidney, ovarian cancers, glioblastoma, and multiple myeloma. These treatments are often used with chemotherapy, as inhibiting angiogenesis can normalize tumor vessels, potentially improving the delivery and effectiveness of other anti-cancer drugs. For instance, bevacizumab, an anti-VEGF agent, has shown to increase overall survival in metastatic colorectal cancer when combined with chemotherapy.
Beyond cancer, antiangiogenic strategies are also applied to certain eye diseases where abnormal blood vessel growth leads to vision impairment. Wet age-related macular degeneration (AMD) is an example, where leaky new blood vessels under the retina cause fluid and blood leakage, leading to vision loss. Anti-VEGF drugs injected directly into the eye have revolutionized wet AMD treatment, preventing vision deterioration in many patients and improving vision for others.
These therapies are being investigated for other ocular conditions, such as diabetic retinopathy and retinal vein occlusion, which involve pathological blood vessel formation. The goal in these eye conditions is to reduce vascular proliferation and vessel permeability, thereby preserving vision. While effective, these ocular treatments typically require regular injections to maintain their therapeutic effect.
Natural Compounds with Antiangiogenic Properties
Research into natural compounds has identified substances found in common foods that show promise in modulating angiogenesis. These compounds, often derived from plants, are being studied for their potential to inhibit blood vessel formation. While not a substitute for conventional medical treatments, these dietary components offer an interesting area of scientific exploration.
Polyphenols, a category of micronutrients found in plants, have garnered attention for their antiangiogenic effects. Resveratrol, a polyphenol present in red wine and grapes, has demonstrated anti-cancer properties by inhibiting angiogenesis in various cancer types. Green tea polyphenols, particularly epigallocatechin-3-gallate (EGCG), are another example, showing antiangiogenic activity alongside antioxidant and anti-inflammatory effects.
Curcumin, a compound from the spice turmeric, has been investigated for its antiangiogenic properties. It has shown beneficial effects in experimental models by inhibiting pathways involved in inflammation and vessel formation. Other natural compounds include quercetin, found in fruits like apples, onions, and leafy green vegetables, and sulforaphane, present in cruciferous vegetables such as broccoli.
Lycopene, a pigment found in fruits like red pepper and tomatoes, has been shown to reduce VEGF levels and inhibit angiogenesis in studies. These natural compounds interfere with cellular processes that contribute to blood vessel growth, such as inhibiting specific signaling pathways or downregulating pro-angiogenic factors. Research, primarily in laboratory and animal models, continues to explore the mechanisms and potential applications of these dietary components.