Overexpression of Allograft Inflammatory Factor-1 Promotes Proliferation of Vascular Smooth Muscle Cells by Cell Cycle Deregulation

Abstract

Allograft inflammatory factor-1 (AIF-1) is not present in normal arteries, but its expression is induced in vascular smooth muscle cells (VSMCs) in several models of arterial injury. The proliferation of VSMCs is a major component of neointimal hyperplasia in many arteriopathies, and the purpose of this study was to determine the role of AIF-1 in the growth of VSMCs. Transfection and constitutive expression of AIF-1 in a primary and a rat VSMC line results in enhanced growth of those cells as measured by cell number and is proportional to the amount of AIF-1 expressed. Constitutive expression of AIF-1 results in a shorter cell cycle, as measured by flow cytometry, and aberrant expression of cell cycle proteins, as determined by Western blot. AIF-1 overexpression also permits growth of these cells in serum-reduced media. Collectively, these data suggest that AIF-1 may participate in the progression of vascular proliferative disease on the basis of its ability to regulate the growth of VSMCs.