Systemic delivery of proresolving lipid mediators resolvin D2 and maresin 1 attenuates intimal hyperplasia in mice

摘要: Vascular injury induces a potent inflammatory response that influences vessel remodeling and patency, limiting long-term benefits of cardiovascular interventions such as angioplasty. Specialized proresolving lipid mediators (SPMs) derived from ω-3 polyunsaturated fatty acids [eicosapentaenoic acid docosahexaenoic (DHA)] orchestrate resolution in diverse settings acute inflammation. We hypothesized systemic administration DHA-derived SPMs [resolvin D2 (RvD2) maresin 1 (MaR1)] would influence mouse model arterial neointima formation (carotid ligation). In vitro, SPM treatment inhibited aortic smooth muscle cell migration (IC₅₀ ≅ nM) to PDGF gradient reduced TNF-α-stimulated p65 translocation, superoxide production, proinflammatory gene expression (MCP-1). vivo, adult FVB mice underwent unilateral carotid artery ligation with RvD2, MaR1, or vehicle (100 ng by intraperitoneal injection at 0, 1, 3, 5, 7 d after ligated arteries 4 d, was associated proliferation neutrophil macrophage recruitment increased polarization M2 macrophages the wall. Neointimal hyperplasia (at 14 d) notably attenuated RvD2 (62%)- MaR1 (67%)-treated mice, respectively. Modulation pathways may offer new opportunities regulate vascular promote homeostasis.