A novel way of therapeutic angiogenesis using an adeno-associated virus-mediated angiogenin gene transfer

Abstract

To develop a novel therapeutic angiogenesis for the treatment of cardiovascular diseases, angiogenin (ANG1) was examined as a potential therapeutic gene. An adeno-associated virus (AAV)-mediated gene delivery system was used to measure the therapeutic efficacy of ANG1. Using a triple cotransfection technique, rAAV-ANG1-GFP, rAAV-VEGF-GFP and rAAV-GFP vectors were produced, which were then used to infect human umbilical vein endothelial cells (HUVECs) in order to evaluate in vitro angiogenic activities. Their protein expressions, tagged with green fluorescent protein (GFP), were monitored by confocal microscopy. The functional activities were measured using woundhealing HUVEC migration assays. The number of migrated cells stimulated by both the expressed ANG1 and the VEGF in rAAV-infected HUVECs increased almost twice the number observed in the expressed GFP control. In vivo angiogenic activities of the expressed ANG1 or VEGF were determined using mouse angiogenesis assays. The angiogenic activities of ANG1 or VEGF expressed in the injected mice were increased by 1.36 and 2.16 times, respectively, compared to those of the expressed GFP control. These results demonstrate that the expressed ANG1 derived from rAAV infection has in vitro and in vivo angiogenic activities and suggest that the rAAV-ANG1 vector is a potential strategy for therapeutic angiogenesis.

L-mimosine and hypoxia can increase angiogenin production in dental pulp-derived cells

“…This challenge has stimulated research in ANGIOGENIN releasing scaffolds in particular for bone regenerative applications. Another strategy is the gene therapy approach [3, 4, 46]. Adeno-associated virus-mediated angiogenin gene transfer showed promising results [46].…”

Engineering Stem Cells for Biomedical Applications

“…For instance, Liu et al, engineered MSCs with angiogenin, which is a heparin-binding protein that interacts with endothelial cells to promote angiogenesis via the induction of a wide range of cellular responses including migration, [211] proliferation, [212] and tube formation. [213] While angiogenin activity is relatively low when compared to VEGF and fibroblast growth factor (FGF), it has a comparable angiogenic activity and reportedly decreases fibrosis thereby making it an ideal candidate for application to myocardial infarction.…”

Angiogenin is involved in lung adenocarcinoma cell proliferation and angiogenesis

“…It interacts with endothelial cells to induce a wide range of cellular responses including migration [15], proliferation [16], and tube formation [17], all of which are essential in the process of angiogenesis. The activity of angiogenin is relatively low as compared with that of vascular endothelial growth factor and basic fibroblast growth factor.…”