Vascular cell apoptosis: cell type-specific modulation by transforming growth factor- XXXX in endothelial cells versus smooth muscle cells.

@entity2533 @entity8652 @entity455 @entity588
BACKGROUND: It is postulated that @entity455 formation and remodeling involves a balance between vascular cell death and cell proliferation. @entity2533 ( @entity2533 ) is a pleiotropic factor expressed within vascular cells that regulates cell growth in a tissue-specific manner. This study tested the hypothesis that the control of vascular cell apoptosis involves cell type-specific regulation by @entity2533 . METHODS AND RESULTS: In response to serum withdrawal, cultured endothelial cells and vascular smooth muscle cells exhibited apoptosis as evidenced by DNA laddering and quantitated by analysis of nuclear chromatin morphology. Addition of @entity2533 to endothelial cells in serum-free media further potentiated the induction of apoptosis in a dose-dependent fashion. Moreover, @entity2533 promoted endothelial cell death despite the presence of 10% serum. However, endothelial cells plated on collagen I were resistant to @entity2533 -induced apoptosis. This antiapoptotic influence of the matrix was mimicked by integrin activation with anti- @entity8652 antibodies and associated with increased expression of the antiapoptotic factor @entity588 . In accord with the hypothesis that the modulation of antiapoptotic gene expression may mediate the effects of @entity2533 and @entity8652 integrins on cell fate, we observed that endothelial cells with constitutive upregulation of @entity588 remained viable despite exposure to @entity2533 in serum-free conditions. In contrast to the proapoptotic effect of @entity2533 in endothelial cells, addition of @entity2533 to vascular smooth muscle cells in serum-free media inhibited apoptosis. CONCLUSIONS: These findings suggest that the effect of cytokines such as @entity2533 on cell fate is contextual and is modulated by cell-matrix interactions in a cell type-specific manner.
