Abstract Aims Identification and treatment of the rupture prone atherosclerotic plaque remains a challenge for reducing the burden of cardiovascular disease. The interconnection of metabolic and inflammatory processes in rupture prone plaques is poorly understood. Herein, we investigate associations between metabolite profiles, inflammatory mediators and vulnerability in carotid atherosclerotic plaques. Methods and results We collected 159 carotid plaques from patients undergoing endarterectomy and measured 165 different metabolites in a targeted metabolomics approach. We identified a metabolite profile in carotid plaques that associated with histologically evaluated vulnerability and inflammatory mediators, as well as presence of symptoms in patients. The distinct metabolite profiles identified in high-risk and stable plaques were in line with different transcription levels of metabolic enzymes in the two groups, suggesting an altered metabolism in high-risk plaques. The altered metabolic signature in high-risk plaques was consistent with a change to increased glycolysis, elevated amino acid utilization and decreased fatty acid oxidation, similar to what is found in activated leucocytes and cancer cells. Conclusion These results highlight a possible key role of cellular metabolism to support inflammation and a high-risk phenotype of atherosclerotic plaques. Targeting the metabolism of atherosclerotic plaques with novel metabolic radiotracers or inhibitors might therefore be valid future approaches to identify and treat the high-risk atherosclerotic plaque.

中文翻译：

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代谢改变区分高风险和稳定的颈动脉粥样硬化斑块

摘要 目的识别和治疗易破裂的动脉粥样硬化斑块仍然是减轻心血管疾病负担的挑战。对易破裂斑块中代谢和炎症过程的相互联系知之甚少。在此，我们研究了代谢物谱、炎症介质和颈动脉粥样硬化斑块易损性之间的关联。方法和结果 我们从接受动脉内膜切除术的患者身上收集了 159 个颈动脉斑块，并以靶向代谢组学方法测量了 165 种不同的代谢物。我们确定了颈动脉斑块中的代谢物谱，其与组织学评估的易损性和炎症介质以及患者症状的存在相关。在高危斑块和稳定斑块中鉴定出的不同代谢物谱与两组代谢酶的不同转录水平一致，表明高危斑块中的代谢发生了改变。高风险斑块中代谢特征的改变与糖酵解增加、氨基酸利用增加和脂肪酸氧化减少一致，类似于在活化的白细胞和癌细胞中发现的变化。结论这些结果强调了细胞代谢在支持炎症和动脉粥样硬化斑块的高风险表型方面可能发挥的关键作用。因此，用新型代谢放射性示踪剂或抑制剂靶向动脉粥样硬化斑块的代谢可能是未来识别和治疗高风险动脉粥样硬化斑块的有效方法。