Tempol therapy attenuates medial smooth muscle cell apoptosis and neointima formation after balloon catheter injury in carotid artery of diabetic rats
| Autor: | Jason DeLeon, Dammanahalli K. Jagadeesha, Francis J. Miller, Ram V. Sharma, Ramesh C. Bhalla, Timothy E. Lindley |
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| Rok vydání: | 2005 |
| Předmět: |
Neointima
Blood Glucose Carotid Artery Diseases Male medicine.medical_specialty Vascular smooth muscle Physiology Apoptosis Fructose Antioxidants Muscle Smooth Vascular Cyclic N-Oxides Rats Sprague-Dawley chemistry.chemical_compound Physiology (medical) Internal medicine medicine Animals Insulin bcl-2-Associated X Protein chemistry.chemical_classification Reactive oxygen species Superoxide business.industry Caspase 3 Balloon catheter Anatomy Rats medicine.anatomical_structure Endocrinology chemistry Diabetes Mellitus Type 2 Proto-Oncogene Proteins c-bcl-2 Caspases Circulatory system cardiovascular system Spin Labels Cardiology and Cardiovascular Medicine business Carotid Artery Injuries Tunica Intima Tunica Media Angioplasty Balloon Blood vessel Artery |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 289(3) |
| ISSN: | 0363-6135 |
| Popis: | Accumulating data support the hypothesis that reactive oxygen species (ROS) play a critical role in the vascular complications observed in diabetes. However, the mechanisms of ROS-mediated vascular complications in diabetes are not clear. We tested the hypothesis that ROS-mediated increase in proapoptotic factor Bax expression leads to medial smooth muscle cell (SMC) apoptosis that is associated with neointima formation. We used a fructose-rich diet for 4 wk to model Type 2 diabetes in rats. SOD mimetic membrane-permeable 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (Tempol, 1 mM) was administered in drinking water to scavenge superoxide starting 1 day before surgery and continued during the duration of the experiment. Vascular injury resulted in a significant increase in medial SMC apoptosis that was associated with neointima formation. The number of medial SMC positive for Bax immunostaining significantly increased in injured arteries compared with uninjured arteries. Superoxide scavenging by Tempol treatment inhibited both the Bax-positive index as well as the apoptotic index of medial SMC in response to vascular injury. Tempol treatment inhibited apoptotic loss of medial SMC, thus increasing their density in the injured arteries. These alterations in the media were associated with a marked decrease in neointima formation in injured arteries. We conclude that Bax expression may play an important role in vascular SMC apoptosis and, finally, that this regulatory mechanism is redox sensitive. |
| Databáze: | OpenAIRE |
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