on August 25, 2003
Published online before print August 25, 2003, doi: 10.1161/01.CIR.0000085164.13439.89
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 3, 2002
From the Departments of Cardiovascular Medicine (T.T., T. Ichiki, K.F., H.O., N.I., S.M., H.S., K.E., A.T.) and Cancer Therapy and Research (T.M.), Kyushu University Graduate School of Medical Sciences, and the Cardiovascular Research Institute and Internal Medicine III (R.S., H.K., T. Imaizumi), Kurume University School of Medicine, Fukuoka, Japan. * To whom correspondence should be addressed. E-mail: ichiki{at}cardiol.med.kyushu-u.ac.jp.
Background--The balance between apoptosis and proliferation of vascular smooth muscle cells (VSMCs) is believed to contribute to the vascular remodeling process. Cyclic AMP response element-binding protein (CREB) is a critical transcription factor for the survival of neuronal cells and T lymphocytes. However, the role of CREB in blood vessels is incompletely characterized. Methods and Results--Nuclear staining with Hoechst 33258 or propidium iodine showed an increase in apoptotic cells with activation of caspase-3 in VSMCs infected with adenovirus expressing the dominant-negative form of CREB (AdCREBM1). Basal expression of Bcl-2 and Bcl-2 promoter activity were decreased by infection with AdCREBM1. Immunohistochemistry revealed that CREB was mainly induced and activated in the neointimal Conclusions--These results suggest that CRE-dependent gene transcription might play an important role in the survival and proliferation of VSMCs. CREB might be a novel transcription factor mediating the vascular remodeling process and a potential therapeutic target for atherosclerotic disease.
Revised on May 5, 2003
Accepted on May 9, 2003
Apoptosis Induced by Inhibition of Cyclic AMP Response Element-Binding Protein in Vascular Smooth Muscle Cells
Tomotake Tokunou MD,
-smooth muscle actin-positive cells of rat carotid artery after balloon injury. Infection with AdCREBM1 suppressed neointimal formation (intima-media ratio) by 33.8% after 14 days of injury, which was accompanied by an increase in apoptosis as indicated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells and a decrease in bromodeoxyuridine incorporation.
Key words: apoptosis • muscle, smooth • vasculature • phosphates • balloon
Related Article:
Circulation 2003 108: 1164-1166.
This article has been cited by other articles:
 |
|
 |
|
  N. Ozgen, J. Guo, Z. Gertsberg, P. Danilo Jr, M. R. Rosen, and S. F. Steinberg Reactive Oxygen Species Decrease cAMP Response Element Binding Protein Expression in Cardiomyocytes via a Protein Kinase D1-Dependent Mechanism That Does Not Require Ser133 Phosphorylation Mol. Pharmacol., October 1, 2009; 76(4): 896 - 902. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Chava, M. Karpurapu, D. Wang, M. Bhanoori, V. Kundumani-Sridharan, Q. Zhang, T. Ichiki, W. C. Glasgow, and G. N. Rao CREB-Mediated IL-6 Expression Is Required for 15(S)-Hydroxyeicosatetraenoic Acid-Induced Vascular Smooth Muscle Cell Migration Arterioscler Thromb Vasc Biol, June 1, 2009; 29(6): 809 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ohtsubo, T. Ichiki, R. Miyazaki, K. Inanaga, I. Imayama, Y. Hashiguchi, J. Sadoshima, and K. Sunagawa Inducible cAMP Early Repressor Inhibits Growth of Vascular Smooth Muscle Cell Arterioscler Thromb Vasc Biol, July 1, 2007; 27(7): 1549 - 1555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kamiya, K. Sakakibara, E. J. Ryer, R. P. Hom, E. B. Leof, K. C. Kent, and B. Liu Phosphorylation of the Cyclic AMP Response Element Binding Protein Mediates Transforming Growth Factor {beta}-Induced Downregulation of Cyclin A in Vascular Smooth Muscle Cells Mol. Cell. Biol., May 1, 2007; 27(9): 3489 - 3498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nomiyama, T. Nakamachi, F. Gizard, E. B. Heywood, K. L. Jones, N. Ohkura, R. Kawamori, O. M. Conneely, and D. Bruemmer The NR4A Orphan Nuclear Receptor NOR1 Is Induced by Platelet-derived Growth Factor and Mediates Vascular Smooth Muscle Cell Proliferation J. Biol. Chem., November 3, 2006; 281(44): 33467 - 33476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fukuyama, T. Ichiki, I. Imayama, H. Ohtsubo, H. Ono, Y. Hashiguchi, A. Takeshita, and K. Sunagawa Thyroid Hormone Inhibits Vascular Remodeling Through Suppression of cAMP Response Element Binding Protein Activity Arterioscler Thromb Vasc Biol, September 1, 2006; 26(9): 2049 - 2055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Pulver-Kaste, C. A. Barlow, J. Bond, A. Watson, P. L. Penar, B. Tranmer, and K. M. Lounsbury Ca2+ source-dependent transcription of CRE-containing genes in vascular smooth muscle Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H97 - H105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Dworet and J. L. Meinkoth Interference with 3',5'-Cyclic Adenosine Monophosphate Response Element Binding Protein Stimulates Apoptosis through Aberrant Cell Cycle Progression and Checkpoint Activation Mol. Endocrinol., May 1, 2006; 20(5): 1112 - 1120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ichiki Role of cAMP Response Element Binding Protein in Cardiovascular Remodeling: Good, Bad, or Both? Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 449 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Barlow, P. Rose, R. A. Pulver-Kaste, and K. M. Lounsbury Excitation-transcription coupling in smooth muscle J. Physiol., January 1, 2006; 570(1): 59 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ono, T. Ichiki, H. Ohtsubo, K. Fukuyama, I. Imayama, Y. Hashiguchi, J. Sadoshima, and K. Sunagawa Critical Role of Mst1 in Vascular Remodeling After Injury Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 1871 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Crespo, J. Martinez-Gonzalez, J. Rius, and L. Badimon Simvastatin inhibits NOR-1 expression induced by hyperlipemia by interfering with CREB activation Cardiovasc Res, August 1, 2005; 67(2): 333 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Martinez-Gonzalez and L. Badimon The NR4A subfamily of nuclear receptors: new early genes regulated by growth factors in vascular cells Cardiovasc Res, February 15, 2005; 65(3): 609 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zhang, C. V. Remillard, I. Fantozzi, and J. X.-J. Yuan ATP-induced mitogenesis is mediated by cyclic AMP response element-binding protein-enhanced TRPC4 expression and activity in human pulmonary artery smooth muscle cells Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1192 - C1201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Sucharov, S. M. Helmke, S. J. Langer, M. B. Perryman, M. Bristow, and L. Leinwand The Ku Protein Complex Interacts with YY1, Is Up-Regulated in Human Heart Failure, and Represses {alpha} Myosin Heavy-Chain Gene Expression Mol. Cell. Biol., October 1, 2004; 24(19): 8705 - 8715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ono, T. Ichiki, K. Fukuyama, N. Iino, S. Masuda, K. Egashira, and A. Takeshita cAMP-Response Element-Binding Protein Mediates Tumor Necrosis Factor-{alpha}-Induced Vascular Smooth Muscle Cell Migration Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1634 - 1639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Pulver, P. Rose-Curtis, M. W. Roe, G. C. Wellman, and K. M. Lounsbury Store-Operated Ca2+ Entry Activates the CREB Transcription Factor in Vascular Smooth Muscle Circ. Res., May 28, 2004; 94(10): 1351 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rius, J. Martinez-Gonzalez, J. Crespo, and L. Badimon Involvement of Neuron-Derived Orphan Receptor-1 (NOR-1) in LDL-Induced Mitogenic Stimulus in Vascular Smooth Muscle Cells: Role of CREB Arterioscler Thromb Vasc Biol, April 1, 2004; 24(4): 697 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E.B. Reusch and D. J. Klemm Cyclic AMP Response Element-Binding Protein in the Vessel Wall: Good or Bad? Circulation, September 9, 2003; 108(10): 1164 - 1166. [Full Text] [PDF]
|
|