Angiogenesis

Angiogenesis is the growth of new blood vessels from pre-existing ones. It is essential for embryonic development, tissue repair, and the female reproductive cycle, and it also contributes to pathology when misregulated.

Process: Initiation is driven by stimuli such as hypoxia, inflammation, or tissue injury, leading to upregulation of pro-angiogenic signals, notably vascular endothelial growth factor (VEGF) family members, fibroblast growth factors (FGFs), PDGF, and angiopoietins. Endothelial cells respond by degrading the basement membrane with matrix metalloproteinases, migrating, and proliferating to form sprouts that extend toward angiogenic cues. These sprouts connect to form lumens and are stabilized by recruitment of pericytes and smooth muscle cells. The mature network may undergo remodeling as needed. Two main growth modes exist: sprouting angiogenesis and intussusceptive angiogenesis (vessel splitting). Notch signaling (DLL4-Notch) helps regulate tip and stalk cell differentiation to control sprouting and branching.

Regulation: Angiogenesis results from a balance between pro-angiogenic and anti-angiogenic factors. Anti-angiogenic molecules such as thrombospondin-1, angiostatin, and endostatin counteract vessel formation. The local tissue environment, extracellular matrix, and mechanical forces further shape vascular architecture.

Clinical relevance: Physiological angiogenesis supports wound healing and menstrual cycling, while pathological angiogenesis contributes to cancer progression, diabetic retinopathy, age-related macular degeneration, rheumatoid arthritis, and other inflammatory conditions.

Therapy and research: Anti-angiogenic therapies target VEGF signaling or other pro-angiogenic pathways and are used in cancer and ocular diseases. Examples include bevacizumab, ranibizumab, and VEGF-trap inhibitors, sometimes in combination with other treatments. Resistance and adverse effects can occur due to the complexity of angiogenic regulation.