Vascular cell apoptosis - Cell type-specific modulation by transforming growth factor-beta(1) in endothelial cells versus smooth muscle cells

Article

关键词: FACTOR-BETA;    ANGIOTENSIN-II;    EXTRACELLULAR-MATRIX;    HYPERTENSIVE RATS;    DNA FRAGMENTATION;    EXPRESSION;    DEATH;    GROWTH-FACTOR-BETA-1;    INHIBITION;    HYPERTROPHY;   

DOI  :  10.1161/01.CIR.99.15.2019

来源: SCIE

【 摘 要 】

Background-It is postulated that vascular lesion formation and remodeling involves a balance between vascular cell death and cell proliferation. Transforming growth factor-beta(1) (TGF-beta(1)) 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 TGF-beta(1). 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 TGF-beta(1) to endothelial cells in serum-free media further potentiated the induction of apoptosis in a dose-dependent fashion. Moreover, TGF-beta(1) promoted endothelial cell death despite the presence of 10% serum. However, endothelial cells plated on collagen I were resistant to TGF-beta(1)-induced apoptosis. This antiapoptotic influence of the matrix was mimicked by integrin activation with anti-Pi antibodies and associated with increased expression of the antiapoptotic factor bcl-2, In accord with the hypothesis that the modulation of antiapoptotic gene expression may mediate the effects of TGF-beta(1) and beta(1) integrins on cell fate, we observed that endothelial cells with constitutive upregulation of bcl-2 remained viable despite exposure to TGF-beta(1) in serum-free conditions. In contrast to the proapoptotic effect of TGF-beta(1) in endothelial cells, addition of TGF-beta(1) to vascular smooth muscle cells in serum-free media inhibited apoptosis. Conclusions-These findings suggest that the effect of cytokines such as TGF-beta(1) on cell fate is contextual and is modulated by cell-matrix interactions in a cell type-specific manner.

【 授权许可】

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