Angiogenesis

Angiogenesis works by growing new capillaries out of blood vessels that already exist: cells lining a nearby vessel detect a shortage of oxygen, loosen their attachments, and sprout a branch towards the tissue that is short of supply. It is distinct from vasculogenesis, which builds the first vessels of an embryo from scratch. In an adult, angiogenesis is mostly dormant and switches on for repair, for the menstrual cycle, and — harmfully — around a growing tumour.

How it works

Tissue that is short of oxygen stabilises a transcription factor called hypoxia-inducible factor, which turns on vascular endothelial growth factor (VEGF). VEGF binds the VEGFR2 receptor on endothelial cells, the flat cells that line every vessel. Four things then happen in sequence:

1. Permeability. The existing vessel becomes leaky, letting plasma proteins into the surrounding tissue to form a temporary scaffold.
2. Degradation. Matrix metalloproteinases digest the basement membrane so endothelial cells can escape the parent vessel.
3. Sprouting. A single “tip” cell leads the new branch along the VEGF gradient; “stalk” cells behind it divide and form the tube.
4. Maturation. Pericytes and smooth muscle wrap the new tube, and blood flow begins. Vessels that never mature regress again.

Nitric oxide, produced by endothelial nitric oxide synthase (eNOS), relaxes the vessel wall and is required for the sprouting step. Fibroblast growth factor and angiopoietins tune the same process.

Why it matters for repair

No new vessel means no delivery of oxygen, glucose, immune cells, or the raw material for collagen. Tendon, ligament, cartilage, and the myotendinous junction heal slowly in part because they are poorly vascularised to begin with. Chronic wounds — diabetic foot ulcers are the standard example — are characterised by a failure of this pathway rather than by a shortage of willing cells.

The same mechanism has a dark side. Solid tumours cannot grow past roughly a millimetre without recruiting their own blood supply, which is why several approved cancer drugs are VEGF blockers.

Why peptides care

Several compounds catalogued on Retapedia are studied specifically because animal work reports a pro-angiogenic effect:

• BPC-157 is reported to activate VEGFR2 through the Akt–eNOS nitric oxide axis in poorly vascularised tissue such as tendon.
• TB-500 binds actin and is described as promoting endothelial cell migration alongside tissue remodelling.
• GHK-Cu is described as supporting angiogenesis as part of a broader skin-remodelling profile.

Human evidence for all three is limited; the angiogenesis findings come overwhelmingly from cell and rodent models. See each article for its graded evidence.

Related concepts

New vessels are one component of the repair programme, not the whole of it. Inflammation recruits the cells that release VEGF in the first place, and tissue repair and wound healing describe what the new supply is used for.