Abstract # 2278 Event # 86:

Scheduled for Friday, June 22, 2007 10:50 AM-11:05 AM: Session 8 (North Main Hall C/D) Symposium

Inflammation and Atherogenesis in Female Cynomolgus Macaques (Macaca fascicularis)

T. C. Register, S. E. Walker, C. A. Shively, M. R. Adams, J. R. Kaplan, S. E. Appt and T. B. Clarkson
Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA
     Inflammation is a key component of many disease processes, and may play a role in the initiation and progression of disease, be a consequence of the disease, or both. Circulating biomarkers with inflammatory and anti-inflammatory characteristics may be useful indicators of disease and metabolism. We have examined the effects of exogenous estrogens and dietary soy protein/isoflavones on circulating biomarkers, atherosclerosis, and tissue inflammation in pre- and post-menopausal female cynomolgus monkeys. In pre-menopausal female monkeys, a diet enriched in soy protein reduced arterial inflammation as well as atherogenesis in comparison to a diet enriched in casein-lactalbumin. Treatment of post-menopausal subjects with estrogen resulted in significant reductions in several key inflammatory mediators as well as atherosclerosis, while dietary isoflavones had a more limited effect on inflammation and atherogenesis. Gene expression of key inflammatory proteins, including monocyte-chemoattractant protein-1 (MCP-1), in the arteries of these animals was associated with atherosclerosis and circulating MCP-1. Longitudinal studies in these monkeys suggest that the serum concentrations of MCP-1 increase in individuals who are developing atherosclerosis, but not in those who do not. The findings provide additional evidence that circulating inflammatory markers (particularly MCP-1) may be useful indicators of atherosclerotic disease progression and responses to treatment in female nonhuman primates.