AIF-1 expression regulates endothelial cell activation, signal transduction, and vasculogenesis.
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.
Tian
Ying
Y
Temple Univ. School of Medicine, Rm. 810, MRB, 3420 N. Broad St., Philadelphia, PA 19140, USA.
Jain
Surbhi
S
Kelemen
Sheri E
SE
Autieri
Michael V
MV
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002417:Cattle; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018919:Neovascularization, Physiologic; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D046509:Tissue Culture Techniques; D014162:Transfection; D054462:p21-Activated Kinases / Q000378:metabolism
C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D018836:Inflammation Mediators; D008840:Microfilament Proteins; C515903:PAK1 protein, human; D054462:p21-Activated Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
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