angiogenez

Angiogenez, or angiogenesis, is the process by which new blood vessels form from pre-existing vasculature. It is essential for embryonic development, normal wound healing, and placental and reproductive processes, and it also contributes to pathological conditions such as cancer and ocular neovascular diseases.

The process is driven by endothelial cells that respond to pro-angiogenic signals. Hypoxia stabilizes the transcription factor HIF-1, which upregulates VEGF and other mediators. VEGF binding to its receptors stimulates endothelial cell proliferation, migration, and increased permeability. Endothelial cells degrade the basement membrane with matrix metalloproteinases, migrate to form sprouts, and then connect to form tubes. Pericytes and smooth muscle cells later stabilize the new vessels and restore the basement membrane.

Angiogenesis is regulated by a balance between pro-angiogenic and anti-angiogenic factors. Major pro-angiogenic signals include vascular endothelial growth factor (VEGF) family, fibroblast growth factors (FGFs), angiopoietins, and transforming growth factor-beta (TGF-β). Anti-angiogenic molecules include thrombospondins, endostatin, and angiostatin. There are also distinct modes of vessel formation, including sprouting angiogenesis and intussusceptive (pillar) angiogenesis; vasculogenesis describes de novo vessel formation during embryogenesis.

Clinical relevance: physiologic angiogenesis supports development and tissue repair, while dysregulated angiogenesis underlies diseases such as cancer, where tumor vessels facilitate growth and metastasis, and ocular diseases such as age-related macular degeneration and diabetic retinopathy. Therapies that inhibit VEGF signaling (for example, bevacizumab, ranibizumab, aflibercept, and ramucirumab) are used in cancer and eye diseases, often with risks of adverse effects. Experimental strategies also seek to promote angiogenesis to enhance tissue regeneration or ischemic repair.

Historically, the concept of angiogenesis was advanced by Judah Folkman in the 1970s, who proposed that tumor growth is dependent on neovascularization. Since then, understanding of the molecular controls and therapeutic targeting of angiogenesis has grown considerably.