Author + information
- Received November 29, 2018
- Revision received April 26, 2019
- Accepted April 27, 2019
- Published online September 23, 2019.
- Shakeel Kautbally, MDa,∗,
- Sophie Lepropre, PhDa,∗,
- Marie-Blanche Onselaer, PhDa,
- Astrid Le Rigoleur, MDa,
- Audrey Ginion, MSa,
- Christophe De Meester de Ravenstein, PhDa,
- Jerome Ambroise, PhDb,
- Karim Z. Boudjeltia, PhDc,
- Marie Octave, MSa,
- Odile Wéra, MSd,
- Alexandre Hego, BScd,
- Joël Pincemail, PhDe,
- Jean-Paul Cheramy-Biene,
- Thierry Huby, PhDf,
- Martin Giera, PhDg,
- Bernhard Gerber, MD, PhDa,h,
- Anne-Catherine Pouleur, MD, PhDa,h,
- Bruno Guigas, PhDi,j,
- Jean-Louis Vanoverschelde, MD, PhDa,h,
- Joelle Kefer, MD, PhDa,h,
- Luc Bertrand, PhDa,
- Cécile Oury, PhDd,
- Sandrine Horman, PhDa,† and
- Christophe Beauloye, MD, PhDa,h,†∗ ()
- aPôle de Recherche Cardiovasculaire, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
- bCenter for Applied Molecular Technologies, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
- cLaboratory of Experimental Medecine (ULB 222 unit), Centre Hospitalier Universitaire de Charleroi, Université Libre de Bruxelles, Charleroi, Belgium
- dLaboratory of Thrombosis and Hemostasis, GIGA-Cardiovascular Sciences, Department of Cardiology, Université de Liège, Liège, Belgium
- eDepartment of Cardiovascular Surgery, Surgical Research Center and Plateform Nutrition Antioxydante et Santé, University Hospital of Liège, Liège, Belgium
- fINSERM UMR_S 1166, Integrative Biology of Atherosclerosis Team, Université Pierre et Marie Curie-Paris 6 and Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France
- gCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands
- hDivision of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
- iDepartment of Parasitology, Leiden University Medical Center, Leiden, the Netherlands
- jDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands
- ↵∗Address for correspondence:
Dr. Christophe Beauloye, Division of Cardiology, Cliniques Universitaires Saint-Luc, Pôle de Recherche Cardiovasculaire, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Avenue Hippocrate, 55 (B1.55.05), 1200 Brussels, Belgium.
• Platelet phosphoACC is a marker for risk stratification in suspected CAD patients. It identifies high-risk CAD patients and correlates with severity of coronary artery calcification.
• The triglycerides/high-density lipoprotein cholesterol ratio is strongly associated with increased phosphoACC in circulating platelets. PhosphoACC is a metabolic signature of the platelet-proatherogenic lipid interplay in CAD patients.
• Phosphorylation and inhibition of acetyl-CoA carboxylase impacts platelet lipid content by down-regulating triglycerides lipid species.
Adenosine monophosphate–activated protein kinase (AMPK) acetyl-CoA carboxylase (ACC) signaling is activated in platelets by atherogenic lipids, particularly by oxidized low-density lipoproteins, through a CD36-dependent pathway. More interestingly, increased platelet AMPK–induced ACC phosphorylation is associated with the severity of coronary artery calcification as well as acute coronary events in coronary artery disease patients. Therefore, AMPK–induced ACC phosphorylation is a potential marker for risk stratification in suspected coronary artery disease patients. The inhibition of ACC resulting from its phosphorylation impacts platelet lipid content by down-regulating triglycerides, which in turn may affect platelet function.
↵∗ Drs. Kautbally and Lepropre contributed equally to this paper and are joint first authors.
↵† Drs. Horman and Beauloye contributed equally to this paper and are joint senior authors.
This work was supported by grants from the Fonds National de la Recherche Scientifique et Médicale (FNRS) (Belgium) and Louvain Foundation (Louvain-La-Neuve, Belgium), and by unrestricted grants from Bayer and AstraZeneca (Belgium). The Division of Cardiology at Cliniques universitaires Saint-Luc, Belgium, has received unrestricted research grants from AstraZeneca, Bayer Healthcare, and Daiichi-Sankyo (Belgium). Drs. Kautbally and Lepropre were supported by the FNRS (Belgium). Drs. Lepropre and Onselaer were supported by grants from the Salus Sanguinis Foundation (UCLouvain, Belgium). Drs. Octave and Wéra have FRIA fellowships from the FNRS (Belgium). Dr. Horman is a research associate, and Drs. Bertrand and Oury are senior research associates at the FNRS (Belgium). Dr. Pouleur is, and Dr. Beauloye was, a clinical master specialist at the FNRS (Belgium). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received November 29, 2018.
- Revision received April 26, 2019.
- Accepted April 27, 2019.
- 2019 The Authors