angiogenese

Angiogenesis, occasionally spelled angiogenese in some languages, is the growth of new blood vessels from pre-existing vasculature. It is a fundamental process in development, wound healing, and female reproductive cycling, and its dysregulation contributes to many diseases.

Two main modes exist: sprouting angiogenesis, where endothelial cells from a parent vessel create a new sprout that forms a capillary network, and intussusceptive angiogenesis, where a existing vessel splits internally to form new lumens. Core steps include degradation of the basement membrane by matrix metalloproteinases, endothelial cell proliferation and directed migration toward pro-angiogenic cues, tube formation, and eventual stabilization by pericytes and smooth muscle cells. Vascular maturation also requires proper remodeling of the extracellular matrix and hemodynamic forces.

Regulation of angiogenesis involves a balance of pro-angiogenic and anti-angiogenic signals. Hypoxia activates hypoxia-inducible factors (HIFs) that upregulate vascular endothelial growth factor (VEGF) and other pro-angiogenic molecules. VEGF-A plays a central role, supported by fibroblast growth factors (FGFs), angiopoietins acting through the Tie2 receptor, and platelet-derived growth factor (PDGF) for mural cell recruitment. Notch signaling helps regulate the selection of tip versus stalk cells and branching. Anti-angiogenic signals include thrombospondin, endostatin, and certain matrix fragments.

Physiological contexts include embryonic development, placental and corpus luteum angiogenesis, and tissue repair. Pathological angiogenesis occurs in cancer, age-related macular degeneration, diabetic retinopathy, and inflammatory diseases, where abnormal vessel growth supports disease progression.

Therapeutic implications focus on anti-angiogenic strategies that target VEGF signaling or angiogenic receptors, used in cancer and ocular diseases. Challenges include resistance, adverse effects, and the exploration of strategies to normalize rather than simply inhibit vasculature.