Secreted Frizzled-related Protein 1 - Angiogenesis

Angiogenesis

The formation of new blood capillaries is an important component of pathological tissue repair in response to ischemia. The angiogenic process is complex and involves endothelial cell (EC) movement and proliferation.

SFRP1 has been shown to have a role in new vascularization after an ischemic event and as a potent angiogenic factor. In vitro SFRP1 modulated the EC angiogenic response (migration, differentiation) and in vivo SFRP1 stimulated neovascularization in plug or tumor models. The directed movements of EC during de novo vessel formation are coordinated through cellular adhesion mechanisms, cytoskeletal reorganization and by association with elevated expression of angiogenic factors such as, the key factor, vascular endothelial growth factor. The regulation of the EC cytoskeleton is critical to EC spreading and motility. SFRP1 was found to have a major role in mediating EC spreading by regulating reorganization of the actin network and focal contact formations.

In vivo data supports a critical role for SFRP1 in ischemia-induced angiogenesis in adults. Using adenovirus-expressing SFRP1, impaired the canonical Wnt/Fzd pathway in the early phase of ischemia and as a result reduced vascular cell proliferation and delayed vessel formation. When SFRP1 was induced specifically in ECs along the kinetics of ischemia repair, a biphasic response was seen: a delay in capillary formation until day 15 and then an increase in vascular formation at day 25. This indicates that SFRP1 can fine tune the outcome of Wnt/Fzd signaling at different steps in the course of neovessel formation.