Altered metabolism distinguishes high-risk from stable carotid atherosclerotic plaques

Lukas Tomas, Andreas Edsfeldt, Inês G. Mollet, Ljubica Perisic Matic, Cornelia Prehn, Jerzy Adamski, Gabrielle Paulsson-Berne, Ulf Hedin, Jan Nilsson, Eva Bengtsson, Isabel Gonçalves, Harry Björkbacka

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

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 We collected 159 carotid plaques from patients undergoing endarterectomy and measured 165 different metabol- and results ites 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.

Original languageEnglish
Pages (from-to)2301-2310
Number of pages10
JournalEuropean Heart Journal
Volume39
Issue number24
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • Atherosclerosis
  • Carotid plaque
  • High-risk plaque
  • Inflammation
  • Metabolism

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