E. S. Lee1,3, A. T. Nguyen3, K. J. Dolan3, Z. Irwin3, A. Rona3, K. M. Samadzadeh3, H. Smothers3, Z. Smit-McBride2, E. S. Lee1,3 1UC Davis,Surgery,Sacramento, CA, USA 2UC Davis,Eye Center,Sacramento, CA, USA 3Sacramento VA Medical Center,Surgery,Mather, CA, USA
Introduction:
Tobacco use is known to contribute to atherosclerosis and vascular disease. An intimate link exists between oxygen tension and inflammation within localized vascular tissue beds and tobacco smoke. However, we believe that vascular tissue response to environmental tobacco smoke is differential and that the infra-renal aorta is more prone to vascular tissue hypoxia. In this study, we sought to establish the presence of hypoxia in vascular segments of rhesus macaque monkeys after tobacco exposure
Methods:
Rhesus macaques were exposed to tobacco smoke exposure 6 hours per day, 5 days per week. Tobacco smoke exposure occurred over a 4 week period. Control monkeys were exposed to filtered air. Tissue and blood collection occurred on the day immediately following the last day of exposure. Cotinine levels were assessed in monkey's plasma via ELISA techniques. The infra-renal aorta and thoracic aorta were collected and vascular segments were snap frozen in liquid nitrogen. Total protein for hypoxia inducible factor-1 alpha (HIF-1α) was assessed using Western Blotting techniques. Comparisons were made between the thoracic aorta and the infra-renal aorta as well as the between aortae exposed to cigarette smoke and filtered room air. A Student’s 2-tailed t-test was used to determine differences and a P<.05 was considered significant.
Results:
Four monkeys were exposed to tobacco smoke and 2 monkeys served as controls. Serum cotinine levels were higher in monkeys exposed to cigarette smoke compared to controls after 30 days of exposure: 54.9±5.0 ng/mL vs. 0.06±.001 ng/mL (P<.01). HIF-1? was found to be expressed greater in the abdominal aortic tissue from monkeys exposed to tobacco smoke 1.08±0.09 compared to the aortic tissue from controls 0.842±0.11 (P=.04). Similarly, HIF-1? was found to be expressed greater in the thoracic aortic tissue from monkeys exposed to tobacco smoke 1.11±0.16 compared to the thoracic aortic tissue from controls 0.818±0.11 (P=.12). Overall in all aortic samples, there was a trend for the abdominal aortic tissue to have greater levels of HIF-1? than the thoracic aorta (Figure).
Conclusion:
These preliminary results establish the presence of hypoxia in the thoracic and abdominal aorta with just minimal exposure of 4 weeks of cigarette smoke. Smoking and hypoxia in the abdominal and thoracic aorta of rhesus macaques provides a framework for future investigations into atherosclerotic plaque formation in this animal model.
