© 2000 American Heart Association, Inc.
Vascular Biology |
Expression of Allograft Inflammatory Factor-1 Is a Marker of Activated Human Vascular Smooth Muscle Cells and Arterial Injury
From the Departments of Physiology and Cardiology, Heart Failure Research Group, Temple University School of Medicine, Philadelphia, Pa.
Correspondence to Michael Autieri, PhD, Departments of Cardiology and Physiology, Temple University School of Medicine, Room 809, MRB, 3420 N Broad St, Philadelphia PA 19140. E-mail mautieri{at}unix.temple.edu
Abstract—The
cytokine-induced activation and proliferation of medial
vascular smooth muscle cells (VSMCs) leading to intimal hyperplasia is
one of the most critical cellular events in the formation of transplant
arteriopathy and balloon 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 AIF-1
expression may be associated with the VSMC response to injury. In this
study, we examined AIF-1 expression in immunologic and mechanical
models of arterial injury. Reverse
transcription–polymerase chain reaction and Western analysis
demonstrated that AIF-1 is acutely and transiently expressed in aortic
medial smooth muscle cells of rat cardiac allografts, with mRNA and
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 cells of the developing neointima. AIF-1 protein
is not expressed in quiescent cultured human VSMCs but is induced in
cells challenged with various inflammatory cytokines, primarily
by interferon-
, interleukin-1ß, and T-cell–conditioned media.
Transfection and overexpression of AIF-1 in human VSMCs result in
enhanced growth of these cells. Taken together, these data indicate
that AIF-1 expression is associated with vascular trauma and suggest
that this protein may play a role in VSMC activation subsequent to
arterial injury.
Key Words: allograft inflammatory factor-1 • vascular smooth muscle cells • cytokines • transplant arteriopathy • balloon angioplasty
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