Submitted on June 19, 2008
Revised on August 21, 2008
Accepted on September 8, 2008
Allograft Inflammatory Factor-1 (AIF-1) Expression Regulates Endothelial Cell Activation, Signal Transduction, and Vasculogenesis
Ying Tian, Surbhi Jain, Sheri Kelemen, and Michael Autieri1*
1 Temple University Medical School
* To whom correspondence should be addressed. E-mail: mautieri{at}temple.edu.
Aims. Endothelial cell (EC) activation plays a key role in vascular inflammation, thrombosis, and angiogenesis. Allograft Inflammatory Factor-1 (AIF-1) is a cytoplasmic, calcium-binding, inflammation-responsive scaffold protein that has been implicated in the regulation of inflammation. The expression and function of AIF-1 in EC is uncharacterized, and the purpose of this study was to characterize AIF-1 expression and function in EC. Methods and Results. AIF-1 expression co-localized with CD31-positive endothelial cells in neointima of inflamed human arteries, but not normal arteries. AIF-1 is detected at low levels in unstimulated EC, but expression can be increased in response to serum and soluble factors. Stable transfection of AIF-1 siRNA in EC reduced AIF-1 protein expression by 73%, and significantly reduced EC proliferation and migration (P<0.05, and 0.001). Rescue of AIF-1 expression restored both proliferation and migration of siRNA expressing ECs, and AIF-1 over expression enhanced both of these activities, suggesting a strong association between AIF-1 expression and EC activation. Activation of MAPK p44/42 and PAK1 was significantly reduced in siRNA ECs challenged with inflammatory stimuli. Reduction of AIF-1 expression did not decrease EC tube-like structure or microvessel formation from aortic rings, but over-expression of AIF-1 did significantly increase the number and complexity of these structures. Conclusions. These data indicate that AIF-1 expression plays an important role in signal transduction and activation of endothelial cells, and may also participate in new vessel formation.
