Key result
Macrophage GLUT1 deletion significantly reduced plasma total and LDL cholesterol but increased necrotic core size and number in atherosclerotic lesions compared to controls.
Why the study?
Macrophages play a key role in atherosclerosis pathogenesis, and preliminary findings suggested macrophage GLUT1 deletion reduces pro-inflammatory responses.
Does macrophage-specific GLUT1 deletion alter atherogenesis and cholesterol metabolism in Ldlr-/- mice?
Does macrophage-specific GLUT1 deletion alter atherogenesis and cholesterol metabolism in Ldlr-/- mice?
Macrophage-specific GLUT1 deletion in Ldlr-/- mice reduces systemic cholesterol but increases necrotic core size in atherosclerotic lesions, suggesting a complex role in lesion stability.
Macrophage GLUT1 deletion may destabilize plaques in mice despite lowering cholesterol; leaves open relevance to human atherogenesis.
Macrophages play a key role in the pathogenesis of atherosclerosis. We recently created a novel murine model with GLUT1 specifically deleted from monocyte/macrophages. Preliminary results from our lab suggest that macrophages lacking GLUT1 reduce the pro-inflammatory response. We therefore hypothesized that macrophages with GLUT1 deletion will have reduced pro-inflammatory activation during atherogenesis, which will reduce formation of atherosclerosis in a mouse model lacking the LDL receptor (Ldlr-/-). We transplanted bone marrow from Glut1fl/fl or Glut1MΦ-/- mice into Ldlr-/- mice and fed mice a Western Diet (WD) for 12 weeks. Glut1MΦ-/- Ldlr-/- mice exhibited significantly less plasma total cholesterol and LDL cholesterol compared to Glut1fl/fl Ldlr-/- mice. Additionally, our results demonstrated that mice with macrophages lacking GLUT1 displayed more and larger necrotic cores in atherosclerotic lesions compared to floxed transplanted controls. These results suggest that macrophage glucose metabolism mediates systemic cholesterol metabolism, and atherogenesis. Importantly, the maintenance of atherosclerotic lesion stability may be regulated by macrophage glucose metabolism-dependent mechanisms.
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Liyang Zhao (2019) studied Atherosclerosis. Macrophage GLUT1 deletion vs. Floxed transplanted controls (Glut1fl/fl) was evaluated on Plasma total cholesterol, LDL cholesterol, and atherosclerotic lesion necrotic cores. Macrophage GLUT1 deletion significantly reduced plasma total and LDL cholesterol but increased necrotic core size and number in atherosclerotic lesions compared to controls.
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