Angiogenesis is the vital physiological process of forming new blood vessels from pre-existing vasculature. It is a tightly regulated process essential for growth, development, and tissue repair in healthy adults, but its dysregulation is a hallmark of many diseases, especially cancer.
Angiogenesis is the vital physiological process of forming new blood vessels from pre-existing vasculature. It is a tightly regulated process essential for growth, development, and tissue repair in healthy adults, but its dysregulation is a hallmark of many diseases, especially cancer. Angiogenesis is a complex, multi-step process primarily driven by the need of a tissue for more oxygen and nutrients (often triggered by hypoxia, or low oxygen levels). Low oxygen levels cause cells to release pro-angiogenic factors, most importantly Vascular Endothelial Growth Factor (VEGF). VEGF binds to receptors (VEGFRs) on the endothelial cells lining the existing blood vessel, activating them. The activated endothelial cells, particularly the leading "tip cells," release proteolytic enzymes (like Matrix Metalloproteinases, MMPs) that degrade the surrounding basement membrane and the extracellular matrix (ECM). The tip cells then migrate into the surrounding tissue, creating a sprout toward the angiogenic stimulus. Stalk cells follow the tip cells, proliferating to elongate the sprout. The sprouts connect with neighboring vessels (anastomosis) to form a new loop. Pericytes (smooth muscle-like cells) are recruited to wrap around the new vessel, providing stability and completing the maturation process.The process is governed by the delicate balance between pro-angiogenic and anti-angiogenic factors.
Pro-Angiogenic VEGF (Vascular Endothelial Growth Factor): The master regulator, stimulating endothelial cell proliferation and migration.
FGF (Fibroblast Growth Factor): Promotes endothelial cell growth and the overall process.
Anti-Angiogenic Angiostatin: Inhibits endothelial cell proliferation.
Thrombospondin-1 (TSP-1): Inhibits the migration of endothelial cells.
Angiogenesis is a beneficial and self-limiting process in normal physiology. It is essential for building the entire vascular system during growth. It is a critical component of the proliferative phase, forming the rich network of capillaries in granulation tissue to supply the wound with oxygen and immune cells. Occurs cyclically in the uterus to build and shed the endometrium during the menstrual cycle. Helps increase blood supply to heart and muscle tissues in response to increased metabolic demand. In disease, angiogenesis is often uncontrolled and excessive, contributing to disease progression. In cancer, tumors cannot grow beyond 1-2 mm in size without a blood supply. They hijack the angiogenic process by secreting massive amounts of pro-angiogenic factors (like VEGF) to build their own disorganized vascular network, which supplies nutrients and provides a route for metastasis (cancer spread). In ocular diseases, excessive and abnormal vessel growth in the eye, such as in Wet Age-Related Macular Degeneration (AMD) or Diabetic Retinopathy, can lead to leakage, hemorrhage, and blindness. In inflammatory diseases, it contributes to the joint damage in conditions like Rheumatoid Arthritis by supplying the inflamed tissue with nutrients and inflammatory cells. The ability to therapeutically modulate angiogenesis by stimulating it for wound healing/ischemic diseases or inhibiting it for cancer/ocular diseases is a major focus of medical research.