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 µM 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.
Highlights
Angiogenesis is a multistep complex process which involves growth of new blood vessels from the existing vasculature
In this report we present the data from in vitro and in vivo studies on the effect of Copper transporter 1 (CTR1) silencing that inhibited angiogenesis by limiting copper entry into endothelial cells
Cytotoxicity assay To test the cytotoxic effect of Cu on human umbilical vein endothelial cells (HUVECs), MTT assay was done by incubating the cells with varying concentrations Cu from 10 nM–1 mM
Summary
Angiogenesis is a multistep complex process which involves growth of new blood vessels from the existing vasculature. This normally occurs in the physiological processes viz reproduction, development, wound healing [1], and in pathological process of inflammation, tumour growth, and neovascularisation [2]. A balance is required between proangiogenic and antiangiogenic factors Towards this end, inhibitors like Bevacizumab targeting VEGF, sorafenib and sunitinib targeting tyrosine kinase receptors are employed for controlling angiogenesis [5]. There is a compelling need for developing molecules that can be used for therapeutic applications to treat angiogenesis related diseases
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