Am J Physiol Cell Physiol AJP: Gastrointestinal and Liver Physiology
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Am J Physiol Cell Physiol 296: C256-C266, 2009. First published September 11, 2008; doi:10.1152/ajpcell.00325.2008
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VASCULAR BIOLOGY

AIF-1 expression regulates endothelial cell activation, signal transduction, and vasculogenesis

Ying Tian,* Surbhi Jain,* Sheri E. Kelemen, and Michael V. Autieri

Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania

Submitted 19 June 2008 ; accepted in final form 8 September 2008

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 ECs. AIF-1 expression colocalized with CD31-positive ECs 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 small interfering RNA (siRNA) in ECs 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 overexpression enhanced both of these activities, suggesting a strong association between AIF-1 expression and EC activation. Activation of mitogen-activated protein kinase 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 overexpression of AIF-1 did significantly increase the number and complexity of these structures. These data indicate that AIF-1 expression plays an important role in signal transduction and activation of ECs and may also participate in new vessel formation.

small interfering RNA; vascular inflammation; allograft inflammatory factor-1



Address for reprint requests and other correspondence: M. Autieri, Temple Univ. School of Medicine, Rm. 810, MRB, 3420 N. Broad St., Philadelphia, PA 19140 (mautieri{at}temple.edu)







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