Figure 1.

Embryonic tendons show a high density of tendon cells producing VEGF, ultimately resulting in a pronounced angiogenic response in developing tendons (A). In healthy adult tendons the relative cell density decreases and tenocytes produce the antiangiogenic factor endostatin in response to physiological mechanical load, thus limiting neo-angiogenesis (B). In diseased tendons, tenocytes produce HIF-1 in response to mechanical overload and/ or hypoxia. HIF-1 in turn induces the expression of VEGF, promoting neoangiogenesis. Hemorrhage due to vascular injury also leads to an increase in VEGF and to the production of matrix metalloproteinases (MMPs), resulting in a further weakening and degradation of the tendon matrix (C).