Thrombospondin 2 deficiency influences extracellular matrix assembly leading to increased ischemia-induced angiogenesis and arteriogenesis.

The extracellular matrix (ECM) protein thrombospondin 2 (TSP2) functions as matricellular protein by modulating cell-ECM interactions. Studies in TSP2-null mice have demonstrated increased angiogenesis in several tissues, especially after injury to tissues. In the present study, we evaluated the ability of TSP2-null mice to respond to ischemia in the hindlimb for a period of 4 wks following excision of the left femoral artery. Measurements of blood flow indicated that, when compared to littermate control mice, TSP2-null mice recovered at an accelerated rate. The observed changes correlated with the temporal expression of TSP2 in ischemic muscle from control mice. Immunohistochemical analysis revealed a dramatic increase in angiogenesis in the TSP2-null ischemic muscle and elevated deposition of MMP9. The latter was confirmed by zymography and western blot of muscle protein extracts. Furthermore, TSP2-null mice displayed increased arteriogenesis determined by angiography. Taken together, our observations implicate TSP2 as an inhibitor of angiogenesis and arteriogenesis in ischemia. [ABSTRACT FROM AUTHOR]