Abstract 10093: Dietary L-Arginine Reduces Aortic Angiogenesis in Atherosclerotic Rabbits
AIM: Evaluate the effect of dietary L-arginine on angiogenesis in the aortic wall of an animal model of early atherosclerosis.
BACKGROUND: Atherosclerosis is associated with increased angiogenesis in the vessel wall, representing vasa vasorum expansion to support atherosclerotic plaque growth. We have developed an αvβ3-integrin targeted nanoparticle contrast agent for molecular imaging of angiogenesis to noninvasively monitor the progression of atherosclerosis with MRI. Cholesterol feeding induces intimal thickening and impairs endothelial function in rabbits, similar to the early progression of atherosclerosis in humans. Cholesterol feeding disrupts nitric oxide activity, a primary endothelial signaling pathway that maintains normal vascular physiology. Dietary L-arginine augments endogenous nitric oxide production and improves endothelial cell function in these animals.
METHODS: Paramagnetic αvβ3-targeted nanoparticles were used to map aortic angiogenesis in vivo with MRI. Rabbits fed a 0.25% cholesterol diet for 60 days received no treatment (n=6) or 2.25% L-arginine in drinking water (n=4) for 24 days. The abdominal or thoracic aorta was imaged on a clinical 1.5T scanner before and 4 hours after injection of αvβ3-targeted nanoparticles. The MRI signal enhancement was calculated in percent based on the signal intensity of the aortic wall before and after nanoparticle injection.
RESULTS: The untreated rabbits displayed higher angiogenesis in the thoracic aorta compared to the abdominal aorta (32.6 ± 1.4% vs. 21.3 ± 1.8% MRI enhancement, p<0.05), consistent with the known distribution of atherosclerosis in this model. Treatment with dietary L-arginine (Figure) significantly reduced angiogenesis in both the thoracic and abdominal aortas (3.9 ± 3.3% and 8.0 ± 1.2%, respectively, p<0.05).
CONCLUSIONS: Dietary L-arginine effectively reduces angiogenesis in both the thoracic and abdominal aorta of this animal model of early atherosclerosis.
- © 2011 by American Heart Association, Inc.