Vascular cell apoptosis: cell type-specific modulation by transforming growth factor-beta1 in endothelial cells versus smooth muscle cells.
BACKGROUND
It is postulated that vascular lesion formation and remodeling involves a balance between vascular cell death and cell proliferation. Transforming growth factor-beta1 (TGF-beta1) 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-beta1.


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-beta1 to endothelial cells in serum-free media further potentiated the induction of apoptosis in a dose-dependent fashion. Moreover, TGF-beta1 promoted endothelial cell death despite the presence of 10% serum. However, endothelial cells plated on collagen I were resistant to TGF-beta1-induced apoptosis. This antiapoptotic influence of the matrix was mimicked by integrin activation with anti-beta1 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-beta1 and beta1 integrins on cell fate, we observed that endothelial cells with constitutive upregulation of bcl-2 remained viable despite exposure to TGF-beta1 in serum-free conditions. In contrast to the proapoptotic effect of TGF-beta1 in endothelial cells, addition of TGF-beta1 to vascular smooth muscle cells in serum-free media inhibited apoptosis.


CONCLUSIONS
These findings suggest that the effect of cytokines such as TGF-beta1 on cell fate is contextual and is modulated by cell-matrix interactions in a cell type-specific manner.
Pollman
M J
MJ
Cardiovascular Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Naumovski
L
L
Gibbons
G H
GH
D000818:Animals; D001011:Aorta; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen; D016895:Culture Media, Serum-Free; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005109:Extracellular Matrix / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D019254:Genes, bcl-2; D006801:Humans; D007231:Infant, Newborn; D019012:Integrin beta1 / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009928:Organ Specificity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014471:Umbilical Veins
D016895:Culture Media, Serum-Free; D019012:Integrin beta1; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta; D003094:Collagen