The Role of Allograft Inflammatory Factor-1 in Development of Coronary Artery Vasculopathy

Allograft inflammatory factor-1 (AIF-1) is a 143-amino acid, cytoplasmic, calcium- binding protein that is expressed in a variety of inflammatory situations. Constitutively expressed in leukocytes, AIF-1 is not expressed in unstimulated vascular smooth muscle cells (VSMCs), but is strongly induced in response to injury and inflammatory cytokines. Overexpression of AIF-1 in VSMCs promotes their proliferation by dysregulation of cell cycle protein expression and subsequent shortening of the cell cycle. In cardiac transplant recipients, the expression of AIF-1 mRNA in cardiac allografts correlates with rejection, and the amount of AIF-1 expressed is proportional to the severity of rejection. AIF-1 is expressed in coronary arteries with cardiac allograft vasculopathy, and persistent expression of AIF-1 in the allograft correlates with development of cardiac allograft vasculopathy. The current hypothesis is that the expression of AIF-1 in injured arteries may participate in the progression of cardiac allograft vasculopathy by its ability to promote growth of VSMCs, implicating AIF-1 as a target for treating proliferative arteriopathies. (c) 2002 Prous Science. All rights reserved.