Ig-like domain 6 of VCAM-1 is a potential therapeutic target in TNFα-induced angiogenesis.
- Author:
Taek Keun KIM
1
;
Chang Sik PARK
;
Hee Jun NA
;
Kangseung LEE
;
Aerin YOON
;
Junho CHUNG
;
Sukmook LEE
Author Information
- Publication Type:Original Article
- MeSH: Animals; Aorta; Arthritis, Rheumatoid; Endothelial Cells; Macular Degeneration; Rats; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1*
- From:Experimental & Molecular Medicine 2017;49(2):e294-
- CountryRepublic of Korea
- Language:Korean
- Abstract: Tumor necrosis factor alpha (TNFα)-induced angiogenesis plays important roles in the progression of various diseases, including cancer, wet age-related macular degeneration, and rheumatoid arthritis. However, the relevance and role of vascular cell adhesion molecule-1 (VCAM-1) in angiogenesis have not yet been clearly elucidated. In this study, VCAM-1 knockdown shows VCAM-1 involvement in TNFα-induced angiogenesis. Through competitive blocking experiments with VCAM-1 Ig-like domain 6 (VCAM-1-D6) protein, we identified VCAM-1-D6 as a key domain regulating TNFα-induced vascular tube formation. We demonstrated that a monoclonal antibody specific to VCAM-1-D6 suppressed TNFα-induced endothelial cell migration and tube formation and TNFα-induced vessel sprouting in rat aortas. We also found that the antibody insignificantly affected endothelial cell viability, morphology and activation. Finally, the antibody specifically blocked VCAM-1-mediated cell–cell contacts by directly inhibiting VCAM-1-D6-mediated interaction between VCAM-1 molecules. These findings suggest that VCAM-1-D6 may be a potential novel therapeutic target in TNFα-induced angiogenesis and that antibody-based modulation of VCAM-1-D6 may be an effective strategy to suppress TNFα-induced angiogenesis.
