Abstract 279: Resolvin D2 and Maresin 1 Modulate Vascular Inflammation, Cell Migration Aad Macrophage Polarization in a Mouse Model of Arterial Injury
Introduction: Vascular injury induces a potent inflammatory response that influences vessel remodeling and patency, limitinglimits the long-term benefits of cardiovascular interventions such as angioplasty. Specialized pro-resolving lipid mediators (SPMs) derived from omega-3 polyunsaturated fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) orchestrate resolution in diverse settings of acute inflammation. We hypothesized that systemic administration of DHA-derived SPMs (resolvin D2 [RvD2] and maresin 1 [MaR1]) would influence vessel remodelinginflammation and remodeling in a mouse model of arterial neointima formation (carotid ligation).
Methods and Results: In-vitro, SPM treatment inhibited mouse aortic smooth muscle cell (SMC) migration (IC50@1 nM) to a PDGF gradient and reduced tumor necrosis factor-α stimulated p65 translocation, superoxide production and pro-inflammatory gene expression (MCP-1). In vivo, adult FVB mice underwent unilateral carotid arteryi ligation with administration of RvD2, MaR1, or vehicle (100ng by intraperitoneal injection at 0, 1, 3, 5 and 7 days post ligation). In ligated carotid arteries at 4 days, SPM treatment was associated with reduced cell proliferation, neutrophil and macrophage recruitment, and increased polarization of M2 macrophages in the arterial wall (M2 macrophage proportion; RvD2 62%, MaR1 51% and control 43%). Neointimal hyperplasia (at 14 days) was notably attenuated in RvD2 (62%) and MaR1 (67%) treated mice, respectively. Proliferating cells at 14 days are mainly SMCs.
Conclusion: Modulation of resolution pathways may offer new opportunities to regulate the vascular injury response and promote vascular homeostasis.
Author Disclosures: D. Akagi: None. M. Chen: None. R. Toy: None. G. Mottola: None. A. Chatterjee: None. M.S. Conte: None.
- © 2015 by American Heart Association, Inc.