Metabolic Impairment in Coronary Artery Disease: Elevated Serum Acylcarnitines Under the Spotlights

Frontiers in Cardiovascular Medicine

Flora Colledge¹  Joséphine Gander²  Lukas Streese²  Henner Hanssen²  Arno Schmidt-Trucksäss²  Denis Infanger²  Raphael Knaier²  Christopher Klenk²  Justin Carrard²  Jonathan Wagner²  Gilles Nève²  Hector Gallart-Ayala³  Rébecca Borreggine³  Julijana Ivanisevic³  Tony Teav³ 

[1] Division of Sports Science, Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland;Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland;Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland;

关键词: metabolomics;    coronary artery disease;    carnitine;    acylcarnitine;    branched-chain amino acids;    fatty acid oxidation (FAO);   

DOI  :  10.3389/fcvm.2021.792350

来源: DOAJ

【 摘 要 】

Coronary artery disease (CAD) remains the leading cause of death worldwide. Expanding patients' metabolic phenotyping beyond clinical chemistry investigations could lead to earlier recognition of disease onset and better prevention strategies. Additionally, metabolic phenotyping, at the molecular species level, contributes to unravel the roles of metabolites in disease development. In this cross-sectional study, we investigated clinically healthy individuals (n = 116, 65% male, 70.8 ± 8.7 years) and patients with CAD (n = 54, 91% male, 67.0 ± 11.5 years) of the COmPLETE study. We applied a high-coverage quantitative liquid chromatography-mass spectrometry approach to acquire a comprehensive profile of serum acylcarnitines, free carnitine and branched-chain amino acids (BCAAs), as markers of mitochondrial health and energy homeostasis. Multivariable linear regression analyses, adjusted for confounders, were conducted to assess associations between metabolites and CAD phenotype. In total, 20 short-, medium- and long-chain acylcarnitine species, along with L-carnitine, valine and isoleucine were found to be significantly (adjusted p ≤ 0.05) and positively associated with CAD. For 17 acylcarnitine species, associations became stronger as the number of affected coronary arteries increased. This implies that circulating acylcarnitine levels reflect CAD severity and might play a role in future patients' stratification strategies. Altogether, CAD is characterized by elevated serum acylcarnitine and BCAA levels, which indicates mitochondrial imbalance between fatty acid and glucose oxidation.

【 授权许可】

Unknown