| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Fraunhofer Institute of Toxicology and Aerosol Research, Department of Molecular Toxicology and Pharmacokinetics, Hannover, Germany; and
Klinik für Thorax-, Herz und Gefäss-Chirurgie, Medical School of Hannover, Hannover, Germany
1Correspondence: Fraunhofer Institute of Toxicology and Aerosol Research, Department of Molecular Toxicology and Pharmacokinetics, Nicolai-Fuchs-Str. 1, D-30659 Hannover, Germany. email: Borlak{at}ita.fhg.de
We investigated the gene expression of the nuclear transcription factors
c/EBP
, GATA-2, and the silencer Oct-1 in conjunction with the gene
expression of all major cytochrome P450 genes and of eNOS in cultures
of endothelial cells of the rat. The purity of cultured endothelial
cells was also confirmed by flow cytometry measurements of PECAM-1, a
surface antigen of endothelial cells. Taken collectively, the gene
expression and flow cytometry studies provide strong evidence for
c/EBP, GATA-2, and Oct-1 to play a key role in the cellular
dedifferentiation of endothelial cells; gene expression of eight
individual CYP genes in conjunction with protein activity could be
significantly increased upon treatment with Aroclor 1254, a
well-documented chemical inducer of a battery of genes. Nevertheless,
the gene expression of c/EBP, GATA-2, and most of the CYP genes was
dramatically reduced (up to 90%) in cell cultures lacking PECAM-1
expression; in strong contrast, expression of the silencer Oct-1 was
massively increased (~14-fold). We thus conclude activation of the
silencer Oct-1 to be strongly correlated with loss of PECAM-1 and eNOS
gene expression, e.g., loss of cellular differentiation and endothelial
function; in conjunction, gene expression of all major P450 isoforms
was dramatically reduced in cultures of dedifferentiated endothelial
cells. This process of cellular dedifferentiation and endothelial
dysfunction was accompanied by down-regulation of endothelial specific
transcription factors.—Thum, T., Haverich, A., Borlak, J. Cellular dedifferentiation of endothelium is linked to activation and
silencing of certain nuclear transcription factors: implications for
endothelial dysfunction and vascular biology.
Key Words: endothelial cells • hepatocytes • gene expression • PECAM-1
This article has been cited by other articles:
|
|
 |
|
  Z. Han, Y. Miwa, H. Obikane, M. Mitsumata, F. Takahashi-Yanaga, S. Morimoto, and T. Sasaguri Aryl hydrocarbon receptor mediates laminar fluid shear stress-induced CYP1A1 activation and cell cycle arrest in vascular endothelial cells Cardiovasc Res, March 1, 2008; 77(4): 809 - 818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dodig, B. Ogunwale, S. Dasarathy, M. Li, B. Wang, and A. J. McCullough Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of {alpha}5beta1-integrin Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G154 - G164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Thum, D. Fraccarollo, P. Galuppo, D. Tsikas, S. Frantz, G. Ertl, and J. Bauersachs Bone marrow molecular alterations after myocardial infarction: Impact on endothelial progenitor cells Cardiovasc Res, April 1, 2006; 70(1): 50 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Scalera, J. Borlak, B. Beckmann, J. Martens-Lobenhoffer, T. Thum, M. Tager, and S. M. Bode-Boger Endogenous Nitric Oxide Synthesis Inhibitor Asymmetric Dimethyl L-Arginine Accelerates Endothelial Cell Senescence Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1816 - 1822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Borlak, I. Schulte, and T. Thum ANDROGEN METABOLISM IN THYMUS OF FETAL AND ADULT RATS Drug Metab. Dispos., June 1, 2004; 32(6): 675 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Wagner, B. Guldenzoph, B. Lienenluke, and M. Hecker CD154/CD40-Mediated Expression of CD154 in Endothelial Cells: Consequences for Endothelial Cell-Monocyte Interaction Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 715 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Thum and J. Borlak Mechanistic Role of Cytochrome P450 Monooxygenases in Oxidized Low-Density Lipoprotein-Induced Vascular Injury: Therapy Through LOX-1 Receptor Antagonism? Circ. Res., January 9, 2004; 94(1): e1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Han, P. J. Boyd, S. Colgan, J. A. Madri, and T. L. Haas Transcriptional Up-regulation of Endothelial Cell Matrix Metalloproteinase-2 in Response to Extracellular Cues Involves GATA-2 J. Biol. Chem., November 28, 2003; 278(48): 47785 - 47791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Lemarie, B. Esposito, A. Tedgui, and S. Lehoux Pressure-Induced Vascular Activation of Nuclear Factor-{kappa}B: Role in Cell Survival Circ. Res., August 8, 2003; 93(3): 207 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Borlak, M. Walles, K. Levsen, and T. Thum VERAPAMIL: METABOLISM IN CULTURES OF PRIMARY HUMAN CORONARY ARTERIAL ENDOTHELIAL CELLS Drug Metab. Dispos., July 1, 2003; 31(7): 888 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. THUM and J. BORLAK Testosterone, cytochrome P450, and cardiac hypertrophy FASEB J, October 1, 2002; 16(12): 1537 - 1549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Hutley, A. C. Herington, W. Shurety, C. Cheung, D. A. Vesey, D. P. Cameron, and J. B. Prins Human adipose tissue endothelial cells promote preadipocyte proliferation Am J Physiol Endocrinol Metab, November 1, 2001; 281(5): E1037 - E1044. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. McCormick, S. G. Eskin, L. V. McIntire, C. L. Teng, C.-M. Lu, C. G. Russell, and K. K. Chittur DNA microarray reveals changes in gene expression of shear stressed human umbilical vein endothelial cells PNAS, July 31, 2001; 98(16): 8955 - 8960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. M. Maniscalco, R. H. Watkins, G. S. Pryhuber, A. Bhatt, C. Shea, and H. Huyck Angiogenic factors and alveolar vasculature: development and alterations by injury in very premature baboons Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L811 - L823. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
