Slc7a11-Mediated Cystine/Glutamate Antiport Reprograms Macrophage Polarization and Ameliorates Atherosclerosis - PubMed
8 hours ago
- #macrophage polarization
- #Slc7a11
- #atherosclerosis
- Slc7a11, a cystine/glutamate antiporter, is upregulated by oxidized low-density lipoprotein and is highly expressed in macrophages of atherosclerotic plaques.
- Overexpression of Slc7a11 in macrophages of ApoE null mice (ApoE-/- Slc7a11MOE) reduced atherosclerotic lesions and increased plaque stability after a 16-week western diet.
- ApoE-/- Slc7a11MOE mice showed unchanged blood lipids, decreased inflammatory cytokines, and increased antioxidant capacity.
- Slc7a11-mediated cystine uptake and glutathione synthesis inhibited M1 macrophage polarization by reducing Stat1 phosphorylation and promoted M2 polarization by enhancing Stat6 phosphorylation.
- Macrophage-targeting lipid nanoparticles loaded with ferrostatin-1 promoted Slc7a11-mediated glutathione synthesis, enhancing plaque stability and ameliorating atherosclerosis progression.
- The findings suggest Slc7a11 plays a critical role in macrophage polarization and could be a novel therapeutic target for atherosclerotic cardiovascular diseases (ASCVDs).