The role of vasculature and angiogenesis for the pathogenesis of degenerative tendons disease

Abstract

More than 100 years ago Wilhelm Roux (1895) introduced the term "functional adaptation to anatomy and physiology". Compared with other organ systems the functional adaptation processes are best identifiable in the locomotor system, like for example in the two types of tendons: traction and gliding tendons. Traction tendons are tendons where the direction of pull is in line with the direction of the muscle (e.g. Achilles tendon). Gliding tendons (e.g. tibialis posterior tendon) change direction by turning around a bony or fibrous hypomochlion. In this region the tendon is subjected to intermittent compressive and shear forces and the extracellular matrix consists of avascular fibrocartilage. Avascularity is considered to be a key factor for the etiology of degenerative tendon disease. The repair capability after repetitive microtrauma is strongly compromised in avascular tissue of gliding tendons. Reduced vascularity is not a specific feature of gliding tendons; several studies have shown that the number and size of blood vessels are largely shortened in the waist of the Achilles tendon. However, histological biopsies from degenerated Achilles tendons and Doppler flow examinations revealed a high blood vessel density in patients with degenerative tendon disease. Angiogenesis is mediated by angiogenic factors and recent studies have shown that the vascular endothelial growth factor (VEGF) is highly expressed in degenerative Achilles tendons, whereas VEGF expression is nearly completely downregulated in healthy tendons. Several factors are able to upregulate VEGF expression in tenocytes: hypoxia, inflammatory cytokines and mechanical load. Since VEGF has the potential to stimulate the expression of matrix metalloproteinases and inhibit the expression of tissue inhibitors of matrix metalloproteinases tissue inhibitor of metalloproteinases (TIMP) in various cell types (e.g. endothelial cells, fibroblasts, chondrocytes), this cytokine might play a significant role for the pathogenetic processes during degenerative tendon disease. An animal experiment in the rabbit has shown that local injection of VEGF reduced the material properties of the Achilles tendon. These experimental findings are in accordance with clinical results that a locally administered (in the area with neovascularization) sclerosing drug (Polidocanol) has a beneficial effect on chronic mid-portion Achilles tendinosis. In conclusion, decreased and increased vascularity might be involved in the pathogenesis of degenerative Achilles tendon disease.