Abstract 268: Resolvin D1 Inhibits Neointimal Formation After Vascular Injury in Mice
Background: Resolvin D1 (RvD1), a docosahexaenoic acid (DHA) - derived lipid mediator generated during the resolution of inflammation, possesses potent anti-inflammatory properties. The present study uses a well defined carotid ligation model to investigate the role of RvD1 in the attenuation of neointimal hyperplasia.
Methods: Left common carotid artery ligation was performed in C57BL/6 mice, RvD1 (10 ng/day) or vehicle control was delivered intravenously for 8 consecutive days. Standard morphometric analysis was performed at 28 days post-ligation. Immunohistochemical characterization of leukocyte infiltration and biochemical characterization of tissue reactive oxygen species were performed at 1, 4, 7, 10 days post-ligation. Chemotaxis experiments were performed using isolated human neutrophils, human coronary artery smooth muscle cells (SMC), and murine thoracic aorta SMC in a standard boyden chamber assay.
Results: RvD1 treatment afforded an early dampened inflammatory response with reduced infiltration of neutrophils and macrophages and lower detectable levels of tissue myeloperoxidase and superoxide within the first 7 days post-ligation. Morphometric analysis at 28 days post-ligation confirmed a markedly attenuated intimal area (8.37 vs. 33.06, P < 0.01) and intimal to media ratio (0.23 vs. 0.83, P < 0.01) in RvD1 animals when compared to control. In addition, intimal SMCs were significantly reduced in RvD1 treatment vs. control (30.91 vs. 41.02, P < 0.01). In vitro chemotaxis experiments indicated RvD1 can significantly inhibit both neutrophil (1.39 vs. 3.6, P < 0.05) and SMC (1.67 vs. 2.32, P < 0.05) migration index to inflammatory stimulus leukotriene B4.
Conclusions: Our results identify the therapeutic potential of RvD1 to attenuate the early inflammatory response, smooth muscle cell migration, and subsequent hyperplasia associated with pathological remodeling following vascular wall insult.
- © 2012 by American Heart Association, Inc.