Abstract
Objective: Recent evidence suggests that specialized lipid mediators derived from polyunsaturated fatty acids control resolution of inflammation. Aberrant remodeling following vascular injury is associated with protracted inflammation. We examined the hypothesis that DHA-derived resolvin D2 (RvD2) and maresin-1 (Mar1), attenuate flow-induced arterial remodeling. Methods and Results: Adult FVB mice (N=30) underwent unilateral carotid arterial ligation with administration of RvD2, Mar1, or vehicle (100ng IP on days 0, 1, 3, 5, 7). In ligated carotid arteries, cell proliferation, neutrophil and macrophage recruitment were significantly reduced at 4d by both active treatments. Neointimal hyperplasia at 14d was attenuated by RvD2 (67%) and Mar1 (62%), respectively (Figure). In-vitro, RvD2 and Mar1 produced dose-dependent inhibition of mouse aortic vascular smooth muscle cell (VSMC) migration (IC50@1 nM) and reduced proinflammatory gene expression (MCP-1). Conclusion: Systemic administration of pro-resolving lipid mediators RvD2 and Mar1 attenuates flow-induced remodeling in mice, likely via effects on leukocyte trafficking and VSMC phenotype.
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