Altered metabolism distinguishes high-risk from stable carotid atherosclerotic plaques

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Karolinska Institute
  • Helmholtz Zentrum München
  • Technical University of Munich
  • Skåne University Hospital
  • Universidade Nova de Lisboa
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Kardiologi
Originalspråkengelska
Sidor (från-till)2301-2310
TidskriftEuropean Heart Journal
Volym39
Utgivningsnummer24
StatusPublished - 2018 jun 21
PublikationskategoriForskning
Peer review utfördJa