Abstract 12064: Temporal Evaluation of Vascular Inflammation with Molecular Imaging of Endothelial Cell Adhesion Molecule Expression in a Non-human Primate Model of Obesity and Insulin Resistance
Background: Obesity and insulin resistance (IR) are associated with elevated plasma markers of inflammation and are risk factors for the development of atherosclerosis. The temporal relation between IR and the vascular inflammatory changes that initiate atherosclerosis is unknown. We hypothesized that vascular inflammation, detected by molecular imaging of adhesion molecule expression, is an early event that coincides with the development of IR in a primate model of obesity.
Methods: Six adult male rhesus macaques were studied at baseline and at 4 month intervals after initiating high-fat diet (HFD) for 1 year. At each interval, intravenous glucose tolerance test (IVGTT), X-ray absorptiometry for truncal fat, ultrasound for intimal-medial thickness (IMT), and blood sampling for biomarker assessment were performed. Contrast ultrasound molecular imaging of endothelial cell activation in the common carotid was performed with microbubbles targeted to P-selectin and VCAM-1.
Results: At 4 months, HFD resulted in a significant increase (p<0.05) in truncal fat (20±10 to 33±11 % of truncal mass), IVGTT insulin concentration (AUC 4026±2126 to 7160±5082 μg/ml x min), and monocyte chemotactic protein-1 concentration (212±155 to 543±239 pg/ml) with all continuing to increase at 12 months. C-reactive protein did not increase until 8 months (0.24±0.12 to 0.76±0.51 μg/ml, p=0.02). Likewise, molecular imaging signal enhancement was not detected until 8 months at which time P-selectin increased 4-fold and VCAM-1 increased 6-fold. Further increase in signal intensity was seen at 12 months (10-fold and 7-fold for P-selectin and VCAM-1, respectively). Increases in IMT were detected only at 12 months and were mild (205±39 to 227±54 μm, p<0.01). Carotid plaque was not detected in any subject.
Conclusions: The development of diet-related obesity and IR are followed soon thereafter by marked pro-inflammatory changes of the vascular endothelium before any substantial change in vessel morphology. Contrast ultrasound molecular imaging provides a method for tissue-specific evaluation of a pro-atherosclerotic phenotype associated with metabolic disease. This approach could potentially be used for early risk assessment and to study risk-modifying interventions.
- © 2010 by American Heart Association, Inc.