SiRNA nanoparticles targeting CaMKIIγ in lesional macrophages improve atherosclerotic plaque stability in mice.

ABSTRACT: Atherosclerotic lesional macrophages express molecules that promote plaque progression, but lack of mechanisms to therapeutically target these molecules represents a major gap in translational cardiovascular research. Here, we tested the efficacy of a small interfering RNA (siRNA) nanoparticle (NP) platform targeting a plaque-destabilizing macrophage molecule-Ca²⁺/calmodulin-dependent protein kinase γ (CaMKIIγ). CaMKIIγ becomes activated in advanced human and mouse plaque macrophages and drives plaque necrosis by suppressing the expression of the efferocytosis receptor MerTK. When macrophage-targeted siCamk2g NPs were administered to Western diet-fed Ldlr ^-/- mice, the atherosclerotic lesions showed decreased CaMKIIγ and increased MerTK expression in macrophage

SUBMITTER: Tao W 

PROVIDER: S-EPMC7476570 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature