Impaired biomechanical properties correlate with neoangiogenesis as well as VEGF and MMP-3 expression during rat patellar tendon healing.

Abstract

Recent studies reveal an important role of vascular endothelial growth factor (VEGF)-induced angiogenesis in degenerative tendon diseases. The way how VEGF influences mechanical properties of the tendons is not well understood yet. We here hypothesized that tendinopathy results in a hypoxia-mediated stimulation of VEGF and that the mechanical stability of the tendon is impaired in an angiogenic process by VEGF-induced matrix metalloproteinases (MMPs). A modified in situ freezing model of patellar tendon was used to create a tendinopathy. 0, 7, 14, and 28 days post-surgical animals were sacrificed and patellar tendons were dissected for biomechanical and immunohistochemical analysis. Native tendons were used as controls. Immunohistochemical staining revealed a peak in HIF-1α stabilization immediately after surgery. Both VEGF and MMP-3 were increased 7 days after surgery. Angiogenesis was also abundant 7 days after surgery. In contrast, biomechanical stability of the tendon was decreased 7 days after surgery. The current results reveal a time-dependent correlation of HIF-1/VEGF-induced and MMP-3-supported angiogenesis with decreased biomechanical properties during tendon healing. The therapeutical modulation of neoangiogenesis by influencing the level of VEGF and MMP-3 might be a promising target for new approaches in degenerative tendon diseases. 30:1952-1957, 2012.