In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 31, No. 7 ( 2011-07), p. 1617-1624
Abstract:
The mature form of human vascular endothelial growth factor-D (hVEGF-D ΔNΔC ) is an efficient angiogenic factor, but its full mechanism of action has remained unclear. We studied the effects of hVEGF-D ΔNΔC in endothelial cells using gene array, signaling, cell culture, and in vivo gene transfer techniques. Methods and Results— Concomitant with the angiogenic and proliferative responses, hVEGF-D ΔNΔC enhanced the phosphorylation of VEGF receptor-2, Akt, and endothelial nitric oxide synthase. Gene arrays, quantitative reverse transcription–polymerase chain reaction, and Western blot revealed increases in VEGF-A, stanniocalcin-1 (STC1), and neuropilin (NRP) 2 expression by hVEGF-D ΔNΔC stimulation, whereas induction with hVEGF-A 165 altered the expression of STC1 and NRP1, another coreceptor for VEGFs. The effects of hVEGF-D ΔNΔC were seen only under high-serum conditions, whereas for hVEGF-A 165 , the strongest response was observed under low-serum conditions. The hVEGF-D ΔNΔC -induced upregulation of STC1 and NRP2 was also evident in vivo in mouse skeletal muscle treated with hVEGF-D ΔNΔC by adenoviral gene delivery. The importance of NRP2 in hVEGF-D ΔNΔC signaling was further studied with NRP2 small interfering RNA and NRP antagonist, which were able to block hVEGF-D ΔNΔC -induced survival of endothelial cells. Conclusion— In this study, the importance of serum and upregulation of NRP2 and STC1 for VEGF-D ΔNΔC effects were demonstrated. Better knowledge of VEGF-D ΔNΔC signaling and regulation is valuable for the development of efficient and safe VEGF-D ΔNΔC -based therapeutic applications for cardiovascular diseases.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/ATVBAHA.111.225961
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2011
detail.hit.zdb_id:
1494427-3
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