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Silencing Myeloid Netrin-1 Induces Inflammation Resolution and Plaque Regression.

Circ Res

August 2021

NYU Cardiovascular Research Center, The Leon H. Charney Division of Cardiology, Department of Medicine, New York University Grossman School of Medicine (M. Schlegel, M. Sharma, E.J.B., A.A.C.N., Y.C., M.S.A., E.M.C., G.J.K., C.v.S., J.G., R.F., C.A.N., L.C.S., D.P., E.A.F., K.J.M.).

Rationale: Therapeutic efforts to decrease atherosclerotic cardiovascular disease risk have focused largely on reducing atherogenic lipoproteins, yet lipid-lowering therapies alone are insufficient to fully regress plaque burden. We postulate that arterial repair requires resolution of a maladaptive immune response and that targeting factors that hinder inflammation resolution will facilitate plaque regression. Objective: The guidance molecule Ntn1 (netrin-1) is secreted by macrophages in atherosclerotic plaques, where it sustains inflammation by enhancing macrophage survival and blocking macrophage emigration.

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