Related Experiment Videos
Effects of active and negative mutants of Ras on rat arterial neointima formation
G Jin1, J Chieh-Hsi Wu, Y S Li
1Department of Bioengineering, The Whitaker Institute of Biomedical Engineering, La Jolla, California 92093-0427, USA.
Background:
Ras protein is a key signal transducer in the cause of cell proliferation. We studied the effects of active and negative mutants of the Ras gene on arterial neointimal formation in rats, with the aim of elucidating the molecular mechanisms regulating restenosis following percutaneous transluminal coronary angioplasty.
Materials And Methods:
AdRasV12 and AdRasN17, the recombinant adenoviruses containing a constitutively active mutant and a dominant negative mutant of Ras, respectively, were used to determine whether Ras is necessary and sufficient to modulate the smooth muscle cell proliferation and neointima formation. Following balloon injury, rat common carotid arteries were treated in their distal half with AdRasV12, AdRasN17, or AdLacZ, with the proximal half used as uninfected control.
Results:
In rat arteries subjected to balloon injury, either uninfected or treated with AdLacZ, there were pronounced SMC proliferation and neointima formation. These changes were markedly augmented by AdRasV12 and reduced by AdRasN17.
Conclusion:
Ras is necessary and sufficient for SMC proliferation and neointima formation and may play a critical role in restenosis following balloon angioplasty.
Insights
Ras is essential for smooth muscle cell proliferation and neointima formation, playing a key role in restenosis after angioplasty. Activating Ras mutants increased arterial neointima, while inhibiting mutants reduced it.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Cell Signaling
Background:
- Ras protein is a critical signal transducer involved in cell proliferation.
- Understanding Ras's role is crucial for addressing restenosis after angioplasty.
Purpose of the Study:
- To investigate the effects of active and negative Ras mutants on arterial neointimal formation in rats.
- To elucidate the molecular mechanisms of Ras in regulating restenosis.
Main Methods:
- Utilized recombinant adenoviruses (AdRasV12 and AdRasN17) carrying active and dominant-negative Ras mutants.
- Administered adenoviruses to rat common carotid arteries post-balloon injury, comparing with AdLacZ and uninfected controls.
Main Results:
- Balloon injury induced significant smooth muscle cell (SMC) proliferation and neointima formation.
- AdRasV12 markedly augmented these changes, while AdRasN17 significantly reduced them.
Conclusions:
- Ras is both necessary and sufficient for SMC proliferation and neointima formation.
- Ras plays a critical role in the pathogenesis of restenosis following balloon angioplasty.