| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
promote growth factor-induced proliferation of human vascular smooth muscle cells
1 Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, MA, USA
2 Pulmonary, Critical Care, and Sleep Division, Tufts-New England Medical Center, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: dbeasley{at}tufts-nemc.org.
Hypoxia is thought to be a stimulus for the excessive proliferation of vascular smooth muscle cells (VSMC) that contributes to pulmonary hypertension, but the mechanisms involved are unknown. Here, we tested whether hypoxia-inducible factor 1-
(HIF-1), a master regulator of the transcriptional response to hypoxia, is involved in the enhanced mitogen-induced proliferative responses of hypoxic VSMC. Exposure to moderate hypoxia (5% O2) enhanced the proliferative responses of human pulmonary artery SMC (HPASMC) to mitogens including platelet-derived growth factor (PDGF), fibroblast growth factor 2 (FGF-2) and epidermal growth factor (EGF), compared with those in normoxia (20% O2). Moderate hypoxia elicited increased cellular HIF-1 levels, shown by Western analysis, and also enhanced PDGF-, FGF-2- and EGF-induced expression of HIF-1. Knockdown of HIF-1 or HIF-1
levels in HPASMC with specific small interfering RNAs (siRNAs) inhibited FGF-2-stimulated proliferation of HPASMC incubated in either 5% or 20% O2, but failed to inhibit the co-mitogenic effect of hypoxia. Knockdown of HIF-1 similarly inhibited PDGF-stimulated proliferation, whereas HIF-2 knockdown had no effect on HPASMC proliferation. Knockdown of HIF-1 expression also inhibited growth factor-induced expression of cyclin A. We conclude that HIF-1 promotes proliferative responses of human VSMC to FGF-2, PDGF, and EGF, by mechanisms that may involve HIF-1-dependent expression of cyclin A, but HIF is apparently not crucial to the enhancement of FGF-2-, PDGF- and EGF-induced proliferation of VSMC that occurs during hypoxia.
This article has been cited by other articles:
|
|
 |
|
  R. Zhang, Y. Wu, M. Zhao, C. Liu, L. Zhou, S. Shen, S. Liao, K. Yang, Q. Li, and H. Wan Role of HIF-1{alpha} in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L631 - L640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Michaud, G. A. Robitaille, J.-P. Gratton, and D. E. Richard Sphingosine-1-Phosphate: A Novel Nonhypoxic Activator of Hypoxia-Inducible Factor-1 in Vascular Cells Arterioscler Thromb Vasc Biol, June 1, 2009; 29(6): 902 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Schultz, V. Murthy, J. B. Tatro, and D. Beasley Prolyl hydroxylase 2 deficiency limits proliferation of vascular smooth muscle cells by hypoxia-inducible factor-1{alpha}-dependent mechanisms Am J Physiol Lung Cell Mol Physiol, June 1, 2009; 296(6): L921 - L927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ricciardi, A. R. Elia, P. Cappello, M. Puppo, C. Vanni, P. Fardin, A. Eva, D. Munroe, X. Wu, M. Giovarelli, et al. Transcriptome of Hypoxic Immature Dendritic Cells: Modulation of Chemokine/Receptor Expression Mol. Cancer Res., February 1, 2008; 6(2): 175 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Ray, S. Arab, Y. Deng, P. Liu, L. Penn, D. W. Courtman, and M. E. Ward Oxygen regulation of arterial smooth muscle cell proliferation and survival Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H839 - H852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Black, J. M. DeVol, and S. Wedgwood Regulation of fibroblast growth factor-2 expression in pulmonary arterial smooth muscle cells involves increased reactive oxygen species generation Am J Physiol Cell Physiol, January 1, 2008; 294(1): C345 - C354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Versari, M. Gossl, D. Mannheim, E. Daghini, O. Galili, C. Napoli, L. O. Lerman, and A. Lerman Hypertension and Hypercholesterolemia Differentially Affect the Function and Structure of Pig Carotid Artery Hypertension, December 1, 2007; 50(6): 1063 - 1068. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Schultz, V. Murthy, J. B. Tatro, and D. Beasley Endogenous interleukin-1{alpha} promotes a proliferative and proinflammatory phenotype in human vascular smooth muscle cells Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2927 - H2934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Stenmark, K. A. Fagan, and M. G. Frid Hypoxia-Induced Pulmonary Vascular Remodeling: Cellular and Molecular Mechanisms Circ. Res., September 29, 2006; 99(7): 675 - 691. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
