COMP-Angl Induces Long-lasting Vascular Enlargement, Blood Flow with Temporal Lymphatic Filopodia in vivo

다국어 초록 (Multilingual Abstract)

Angiopoietin-1(Ang1) is a promising growth factor for therapeutic angiogenesis for ischemic tissues. The cardinal feature of Ang1-induced vascular remodeling in vivo is the enlargement of blood vessels in normal and ischemic tissues. However, little is known about the mechanisms involved in the vascular enlargement process or the specific characteristics of the enlarged vessels. Here, we examined changes in vascular remodeling in mouse trachea by systemic protein and adenoviral delivery of a soluble, stable and potent Ang1 variant, COMP-Ang1. Long-term and sustained exposure to COMP-Ang1 induced long-lasting enlargement of postcapillary venules, terminal arterioles and lymphatics with enhanced blood flow, while short-term exposure induced reversible enlargement of the vessels. COMP-Ang1-induced lymphatic enlargement and filopodia were dependent on circulating COMP-Ang1. The vascular enlargement induced by COMP-Ang1 was a result of endothelial cell proliferation. Auto-amplification of Tie2 expression could be involved in the permanent vascular enlargement induced by COMP-Ang1. Enhanced pericyte recruitment was not a feature of COMP-Ang1-induced vascular enlargement. Thus, long-lasting vascular and lymphatic enlargements could be achieved by long-term and sustained exposure of Ang1 above a certain threshold time and level.
Interestingly, the mice received COMP-Ang1 showed promoted wound healing in punched hole injury of ear with enhanced angiogenesis and lymphangiogenesis. Moreover, diabetic mice received COMP-Ang1 showed promoted wound healing in full thickness wound with enhanced blood flow. Therefore, we conclude that COMP-Ang1 could be beneficial growth factor for alleviating ischemic tissues and promoting wound healing.