Neovascularization

Neovascularization is the process by which new blood vessels form from pre-existing vasculature or through vasculogenesis. It occurs in normal development and tissue repair and in various disease states where vessel growth is excessive or abnormal. Physiological neovascularization supports growth, development, wound healing, and reproductive cycles, while pathological neovascularization can contribute to tissue damage and disease progression.

Physiological neovascularization includes sprouting angiogenesis and intussusceptive angiogenesis. Endothelial cells respond to hypoxia and growth factors, most notably vascular endothelial growth factor (VEGF). Basement membranes are degraded by matrix metalloproteinases, endothelial cells proliferate and migrate to form tubular networks, and newly formed vessels are stabilized by pericytes and extracellular matrix.

Regulation of neovascularization involves a balance between pro-angiogenic and anti-angiogenic signals. VEGF signaling through VEGFR2 is central, with hypoxia-inducible factors upregulating VEGF expression. Notch signaling influences sprout formation and vessel patterning, while angiopoietins and the Tie2 receptor regulate maturation and stability. Endogenous inhibitors such as thrombospondin and angiostatin help restrain vessel growth to maintain tissue homeostasis.

Pathological neovascularization is a hallmark of diseases such as cancer, where tumors recruit a blood supply to grow and potentially metastasize, and ocular disorders like diabetic retinopathy and age-related macular degeneration, where fragile, leaky vessels can cause edema and vision loss.

Detection and treatment rely on imaging modalities such as fluorescein angiography and optical coherence tomography, and on therapies including anti-angiogenic agents that inhibit VEGF, laser therapy, or, in selected cases, surgery. Controlling the underlying condition is also important in managing pathological neovascularization.