SNX17 knockdown improves post-ischemic angiogenesis via blocking lysosomal dependent VEGFR degradation

The treatment options for critical limb ischemia (CLI) are limited, and existing methods are often ineffective in restoring microvascular blood supply. We recently explored the association of sorting nexin 17 (SNX17) with angiogenesis. Knockdown of SNX17 promotes angiogenesis and increased blood flow in hindlimb from hindlimb ischemia mice, accompanied with a higher limb salvage rate. This phenomenon can be attributed to the critical role of SNX17 in the degradation of some angiogenic factor receptors, including vascular endothelial growth factor receptor (VEGFR). The linkage between VEGFR and SNX17 facilitates its trafficking to lysosomal degradation. In the absence of SNX17, VEGFR accumulates in early endosomes, leading to prolonged and intensified activation, and consequently promoting angiogenesis. The current study shows that SNX17 plays an important role in angiogenesis by regulating the stability of angiogenic factor receptors, such as VEGFR, and presents a new strategy for facilitating tissue repair in ischemic environments.