Scholarlink

<p>Atherosclerotic plaque rupture results from inflammatory amplification and extracellular matrix degradation rather than lipid accumulation alone. The quantitative contribution of immunometabolism reprogramming to plaque instability remains insufficiently defined. We investigated whether hexokinase-2 (HK2)–mediated glycolytic activation of CD4⁺ T cells function as a mechanistically relevant contributor to plaque destabilization. CD4⁺ T cells were isolated from carotid endarterectomy specimens (<i>n</i> = 120; stable <i>n</i> = 60, unstable <i>n</i> = 60). HK2 expression, enzyme kinetics, metabolic flux, cytokine secretion, MMP-9 activity, and collagen content were quantified and integrated into a nonlinear dynamical systems model. Unstable plaques exhibited a 2.31-fold increase in HK2 expression and a 54.8% increase in catalytic capacity, accompanied by a 62% rise in glycolytic flux and reduced oxidative phosphorylation. Enhanced glycolysis strongly correlated with increased IFN-γ and IL-17 production and a 2.1-fold increase in MMP-9 activity, resulting in a 38% reduction in collagen content. The metabolic amplification coefficient exceeded the stability threshold (𝓡<sub>met</sub> = 1.84), and stochastic simulations predicted high probability of structural destabilization once this threshold was crossed. These findings identify HK2-driven glycolysis as a quantitative contributor to plaque instability and a potential therapeutic target in atherosclerosis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Hexokinase-2–Driven Glycolytic Reprogramming of CD4⁺ T Cells Governs Inflammatory Amplification and Plaque Instability in Human Atherosclerosis

  • 期刊论文

  • 发表日期：

    2026年4月28日

查看全文
  • Manashi Sengupta,
  • Mrinmoy Basak,
  • Pranveer Singh Satvat,
  • Ananya Kalita,
  • Ankur Pan Saikia

摘要

Atherosclerotic plaque rupture results from inflammatory amplification and extracellular matrix degradation rather than lipid accumulation alone. The quantitative contribution of immunometabolism reprogramming to plaque instability remains insufficiently defined. We investigated whether hexokinase-2 (HK2)–mediated glycolytic activation of CD4⁺ T cells function as a mechanistically relevant contributor to plaque destabilization. CD4⁺ T cells were isolated from carotid endarterectomy specimens (n = 120; stable n = 60, unstable n = 60). HK2 expression, enzyme kinetics, metabolic flux, cytokine secretion, MMP-9 activity, and collagen content were quantified and integrated into a nonlinear dynamical systems model. Unstable plaques exhibited a 2.31-fold increase in HK2 expression and a 54.8% increase in catalytic capacity, accompanied by a 62% rise in glycolytic flux and reduced oxidative phosphorylation. Enhanced glycolysis strongly correlated with increased IFN-γ and IL-17 production and a 2.1-fold increase in MMP-9 activity, resulting in a 38% reduction in collagen content. The metabolic amplification coefficient exceeded the stability threshold (𝓡met = 1.84), and stochastic simulations predicted high probability of structural destabilization once this threshold was crossed. These findings identify HK2-driven glycolysis as a quantitative contributor to plaque instability and a potential therapeutic target in atherosclerosis.