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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1217.)
© 2004 American Heart Association, Inc.

Vascular Biology

AIF-1 Expression Modulates Proliferation of Human Vascular Smooth Muscle Cells by Autocrine Expression of G-CSF

Xing Chen; Sheri E. Kelemen; Michael V. Autieri

From the Departments of Physiology (X.C., M.V.A.) and Cardiology (S.E.K.), Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Penn.

Correspondence to Michael Autieri, PhD, Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, Room 810, MRB, 3420 N. Broad St., Philadelphia PA 19140. E-mail mautieri{at}temple.edu

Objective— Allograft inflammatory factor-1 (AIF-1) is associated with vascular smooth muscle cell (VSMC) activation and vascular injury. The purpose of this study was to characterize the molecular mechanism of AIF-1 growth-enhancing effects in human VSMC.

Methods and Results— Primary human VSMCs were stably transduced with AIF-1 retrovirus (RV). Impact on cell growth was evaluated by the increase in cell number, and the effects on gene expression were determined by cDNA microarray analysis. AIF-RV overexpressing cells grew significantly more rapidly than empty-RV control cells in growth medium and serum-reduced medium (P<0.01 and 0.02, respectively). cDNA microarray analysis and Western blotting on serum-starved AIF-1–transduced VSMCs identified increased mRNA expression of several cell cycle proteins and, surprisingly, the cytokine G-CSF. Addition of G-CSF caused a 75% increase in proliferation of VSMCs in the absence of serum growth factors. The proliferative effects of AIF-1 were abrogated by neutralizing antibodies to G-CSF (P<0.05), and AIF-1–transduced VSMCs are chemotactic for human monocytes. Increased expression of G-CSF and colocalization with AIF-1 positive cells were seen in diseased, not normal human coronary arteries.

Conclusions— This study indicates that AIF-1 enhances VSMC growth by autocrine production of G-CSF, and AIF-1 expression may influence VSMC–inflammatory cell communication.

Human VSMCs that overexpress AIF-1 grow more rapidly and express G-CSF. G-CSF is capable of promoting VSMC proliferation, and AIF-1–transduced VSMCs are chemotactic for monocytes. This study indicates that AIF-1 enhances VSMC growth by autocrine production of G-CSF, and AIF-1 expression may influence VSMC–inflammatory cell communication.

Key Words: allograft inflammatory factor-1 • G-CSF • proliferation

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