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<p>Glutaminase-1 (GLS1) converts glutamine to glutamate, fueling anaplerosis, redox defense, and biosynthesis. We synthesize animal, cellular, and human (bulk/single-cell) data to define cell- and stage-specific roles of GLS1 in atherosclerosis and to outline translational opportunities. In early disease, GLS1 drives vascular smooth muscle proliferation, endothelial sprouting, and inflammatory macrophage activation, promoting plaque growth and neovascularization. In advanced plaques, GLS1 sustains fibrous-cap VSMC survival, endothelial barrier function, and macrophage efferocytosis, limiting necrosis and enhancing stability; excessive glutamate may favor calcification. We also connect GLS1 to vascular senescence and ferroptosis. We propose precision use of GLS1 modulation: a proof-of-concept strategy is short-term telaglenastat (CB-839) after angioplasty to curb neointimal hyperplasia, guided by glutamine-PET and biomarkers to avoid destabilizing mature plaques. GLS1 emerges as a tunable metabolic checkpoint whose effects depend on cell state and disease stage; judicious, time-limited modulation could complement lipid-lowering and anti-inflammatory therapies in cardiovascular disease.</p> Graphical Abstract <p></p>

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Glutaminase 1 in Vascular Disease: Linking Metabolic Reprogramming to Atherosclerosis Progression and Stability

  • 期刊论文

  • 发表日期：

    2026年3月11日

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  • Xi-Long Zheng,
  • Hao Yin,
  • Zhihan Tang,
  • Zhixin Shan,
  • Xiaoyan Dai

摘要

Glutaminase-1 (GLS1) converts glutamine to glutamate, fueling anaplerosis, redox defense, and biosynthesis. We synthesize animal, cellular, and human (bulk/single-cell) data to define cell- and stage-specific roles of GLS1 in atherosclerosis and to outline translational opportunities. In early disease, GLS1 drives vascular smooth muscle proliferation, endothelial sprouting, and inflammatory macrophage activation, promoting plaque growth and neovascularization. In advanced plaques, GLS1 sustains fibrous-cap VSMC survival, endothelial barrier function, and macrophage efferocytosis, limiting necrosis and enhancing stability; excessive glutamate may favor calcification. We also connect GLS1 to vascular senescence and ferroptosis. We propose precision use of GLS1 modulation: a proof-of-concept strategy is short-term telaglenastat (CB-839) after angioplasty to curb neointimal hyperplasia, guided by glutamine-PET and biomarkers to avoid destabilizing mature plaques. GLS1 emerges as a tunable metabolic checkpoint whose effects depend on cell state and disease stage; judicious, time-limited modulation could complement lipid-lowering and anti-inflammatory therapies in cardiovascular disease.

Graphical Abstract