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2015 ; 29
(6
): 2504-13
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Systemic delivery of proresolving lipid mediators resolvin D2 and maresin 1
attenuates intimal hyperplasia in mice
#MMPMID25777995
Akagi D
; Chen M
; Toy R
; Chatterjee A
; Conte MS
FASEB J
2015[Jun]; 29
(6
): 2504-13
PMID25777995
show ga
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 ?-3 polyunsaturated fatty acids [eicosapentaenoic acid 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 remodeling in a
mouse model of arterial neointima formation (carotid ligation). In vitro, SPM
treatment inhibited mouse aortic smooth muscle cell migration (IC?? ? 1 nM) to a
PDGF gradient and reduced TNF-?-stimulated p65 translocation, superoxide
production, and proinflammatory gene expression (MCP-1). In vivo, adult FVB mice
underwent unilateral carotid artery ligation with administration of RvD2, MaR1,
or vehicle (100 ng by intraperitoneal injection at 0, 1, 3, 5, and 7 d after
ligation). In ligated carotid arteries at 4 d, SPM treatment was associated with
reduced cell proliferation and neutrophil and macrophage recruitment and
increased polarization of M2 macrophages in the arterial wall. Neointimal
hyperplasia (at 14 d) was notably attenuated in RvD2 (62%)- and MaR1
(67%)-treated mice, respectively. Modulation of resolution pathways may offer new
opportunities to regulate the vascular injury response and promote vascular
homeostasis.