CTR1 Silencing Inhibits Angiogenesis by Limiting Copper Entry into Endothelial Cells

Abstract

Increased levels of intracellular copper stimulate angiogenesis in human umbilical vein endothelial cells (HUVECs). Copper transporter 1 (CTR1) is a copper importer present in the cell membrane and plays a major role in copper transport. In this study, three siRNAs targeting CTR1 mRNA were designed and screened for gene silencing. HUVECs when exposed to 100 mM copper showed 3 fold increased proliferation, migration by 1.8- fold and tube formation by 1.8- fold. One of the designed CTR1 siRNA (si 1) at 10 nM concentration decreased proliferation by 2.5- fold, migration by 4- fold and tube formation by 2.8- fold. Rabbit corneal packet assay also showed considerable decrease in matrigel induced blood vessel formation by si 1 when compared to untreated control. The designed si 1 when topically applied inhibited angiogenesis. This can be further developed for therapeutic application