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Akt controls vascular smooth muscle cell proliferation in vitro and in vivo by delaying G1/S exit
- Source :
- Circulation research. 93(11)
- Publication Year :
- 2003
-
Abstract
- Constitutive activation of serine/threonine kinase Akt causes uncontrolled cell-cycle progression in different cell types and in malignancy. To investigate how Akt activation modulates cell-cycle progression in vascular smooth muscle cells (SMCs) in vitro and in the intact animal, we inhibited Akt-dependent signaling by adenovirus-mediated transfection of a dominant-negative Akt mutant (AA-Akt). We observed reduced proliferation rate ( P P P P Cip1 expression, as demonstrated by lack of effect of AA-Akt on cell proliferation in p21 −/− mouse SMCs. In conclusion, this study demonstrates that Akt-dependent signaling enhances cell-cycle progression of nontransformed SMCs in vitro and in response to vascular injury in the intact animal. These results suggest a role for Akt signaling in modulating the response of normal tissues to stress and the response of the arterial wall to acute and possibly repetitive injuries that ultimately contribute to restenosis and atherosclerosis.
- Subjects :
- Neointima
Cyclin-Dependent Kinase Inhibitor p21
Male
Vascular smooth muscle
Physiology
Biology
Protein Serine-Threonine Kinases
Muscle, Smooth, Vascular
Adenoviridae
S Phase
Rats, Sprague-Dawley
Mice
In vivo
Cyclins
Proto-Oncogene Proteins
medicine
Animals
Carotid Stenosis
Protein kinase B
Cells, Cultured
Genes, Dominant
Mice, Knockout
Cell growth
G1 Phase
Graft Occlusion, Vascular
Ribosomal Protein S6 Kinases, 70-kDa
Transfection
Blood Proteins
Genetic Therapy
Cell cycle
Rats
Disease Models, Animal
medicine.anatomical_structure
Immunology
Cancer research
Cardiology and Cardiovascular Medicine
Proto-Oncogene Proteins c-akt
Angioplasty, Balloon
Cell Division
Blood vessel
Signal Transduction
Subjects
Details
- ISSN :
- 15244571
- Volume :
- 93
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Circulation research
- Accession number :
- edsair.doi.dedup.....107993f6cf92d512876d5b9d001088e6