Expression of allograft inflammatory factor-1 is a marker of activated human vascular smooth muscle cells and arterial injury

The cytokine-induced activation and proliferation of medial vascular smooth muscle cells (VSMCs) leading to intimal hyperplasia is one of the most cri tical cellular events in the formation of transplant arteriopathy and ballo on angioplasty-induced restenosis. Allograft inflammatory factor-1 (AIF-1) is a calcium-binding protein that we have previously shown to be expressed in balloon angioplasty-injured rat carotid arteries. We hypothesized that A IF-1 expression may be associated with the VSMC response to injury. In this study, we examined AIF-1 expression in immunologic and mechanical models o f arterial injury. Reverse transcription-polymerase chain reaction and West ern analysis demonstrated that AIF-1 is acutely and transiently expressed i n aortic medial smooth muscle cells of rat cardiac allografts, with mRNA an d protein peaking at 3 to 7 days after transplant and declining by 10 days after transplant. Immunohistochemical analysis identified abundant AIF-1 in the medial VSMCs of these vessels, Immunohistochemical analysis of balloon angioplasty-injured swine coronary arteries also demonstrates an acute AIF -1 expression detectable by 24 hours and continuing up to 14 days after the procedure. AIF-1 in these vessels also localizes to the medial VSMCs and c ells of the developing neointima. AIF-1 protein is not expressed in quiesce nt cultured human VSMCs but is induced in cells challenged with various inf lammatory cytokines, primarily by interferon-gamma, interleukin-1 beta, and T-cell-conditioned media. Transfection and overexpression of AIF-1 in huma n VSMCs result in enhanced growth of these cells. Taken together, these dat a indicate that AIF-1 expression is associated with vascular trauma and sug gest that this protein may play a role in VSMC activation subsequent to art erial injury.