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Altered metabolism distinguishes high-risk from stable carotid atherosclerotic plaques

Tomas, Lukas LU ; Edsfeldt, Andreas LU ; Mollet, Inês G LU ; Perisic Matic, Ljubica; Prehn, Cornelia; Adamski, Jerzy; Paulsson-Berne, Gabrielle; Hedin, Ulf; Nilsson, Jan LU and Bengtsson, Eva LU , et al. (2018) In European Heart Journal 39(24). p.2301-2310
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... (More)

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.

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@article{9901d387-2b28-4e96-8e77-8cc478f30751,
  abstract     = {<p>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.</p><p>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.</p><p>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.</p>},
  author       = {Tomas, Lukas and Edsfeldt, Andreas and Mollet, Inês G and Perisic Matic, Ljubica and Prehn, Cornelia and Adamski, Jerzy and Paulsson-Berne, Gabrielle and Hedin, Ulf and Nilsson, Jan and Bengtsson, Eva and Gonçalves, Isabel and Björkbacka, Harry},
  issn         = {1522-9645},
  language     = {eng},
  month        = {06},
  number       = {24},
  pages        = {2301--2310},
  publisher    = {Oxford University Press},
  series       = {European Heart Journal},
  title        = {Altered metabolism distinguishes high-risk from stable carotid atherosclerotic plaques},
  url          = {http://dx.doi.org/10.1093/eurheartj/ehy124},
  volume       = {39},
  year         = {2018},
}