Author + information
- Received January 30, 2019
- Revision received January 15, 2020
- Accepted January 15, 2020
- Published online April 27, 2020.
- Mia Ståhle, MSca,
- Johanna M.U. Silvola, PhDa,
- Sanna Hellberg, PhDa,
- Margreet de Vries, PhDb,
- Paul H.A. Quax, PhDb,
- Jeffrey Kroon, PhDc,
- Petteri Rinne, PhDd,e,
- Alwin de Jong, MScb,
- Heidi Liljenbäck, MSca,e,
- Nina Savisto, PhDa,
- Anna Wickman, PhDf,
- Erik S.G. Stroes, MD, PhDc,g,
- Seppo Ylä-Herttuala, MD, PhDh,
- Pekka Saukko, MD, PhDi,
- Tommy Abrahamsson, MD, PhDj,
- Knut Pettersson, PhDj,
- Juhani Knuuti, MD, PhDa,k,
- Anne Roivainen, PhDa,e and
- Antti Saraste, MD, PhDa,k,l,m,∗ ()
- aTurku PET Centre, University of Turku, Turku, Finland
- bEinthoven Laboratory for Experimental Vascular Medicine, Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
- cDepartment of Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, the Netherlands
- dResearch Center for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland
- eTurku Center for Disease Modeling, University of Turku, Turku, Finland
- fi3tex AB, Gothenburg, Sweden
- gDepartment of Vascular Medicine, Academic Medical Center, Amsterdam University Medical Center (UMC), Amsterdam, the Netherlands
- hA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
- iDepartment of Pathology and Forensic Medicine, University of Turku, Turku, Finland
- jAthera Biotechnologies AB, Stockholm, Sweden
- kTurku PET Centre, Turku University Hospital, Turku, Finland
- lHeart Center, Turku University Hospital, Turku, Finland
- mInstitute of Clinical Medicine, Turku University Hospital, Turku, Finland
- ↵∗Address for correspondence:
Dr. Antti Saraste, Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, FI-20520 Turku, Finland.
• Phosphorylcholine is a pro-inflammatory epitope in atherogenic oxidized phospholipids.
• This study investigated effects of a novel monoclonal IgG1 antibody against PC on vascular function and atherosclerotic inflammation.
• Treatment with phosphorylcholine antibody preserved coronary flow reserve and decreased uptake of 18F-FDG in atherosclerotic lesions in hypercholesterolemic mice.
• Noninvasive imaging techniques represent translational tools to assess the efficacy of phosphorylcholine-targeted therapy on coronary artery function and atherosclerosis.
This study showed that treatment with a therapeutic monoclonal immunoglobulin-G1 antibody against phosphorylcholine on oxidized phospholipids preserves coronary flow reserve and attenuates atherosclerotic inflammation as determined by the uptake of 18F-fluorodeoxyglucose in atherosclerotic mice. The noninvasive imaging techniques represent translational tools to assess the efficacy of phosphorylcholine-targeted therapy on coronary artery function and atherosclerosis in clinical studies.
- coronary flow reserve
- 18F-fluorodeoxyglucose positron emission tomography
The study was conducted within the Finnish Centre of Excellence in Cardiovascular and Metabolic Diseases supported by the Academy of Finland, University of Turku, Turku University Hospital, Åbo Akademi University, the European Union’s Seventh Framework Program Project CARDIMMUN (grant 601728), and the European Union Horizon 2020 research and innovation program REPROGRAM (grant agreement 667837). Ms. Ståhle and Drs. Roivainen, and Saraste were supported by the Finnish Foundation for Cardiovascular Research. Drs. Roivainen and Saraste were supported by the Sigrid Jusélius Foundation. Ms. Ståhle was supported by the Instrumentarium Science Foundation, the Finnish Cultural Foundation, and the Drug Research Doctoral Programme, University of Turku Graduate School, Turku, Finland. Dr. Kroon was supported by the Netherlands Organization for Scientific Research VENI (91619098). Drs. Pettersson and T. Abrahamsson have received consultancy fees from and hold shares in Athera Biotechnologies AB. Dr. Pettersson is named as co-inventor on patent applications regarding therapeutic antibodies to PC assigned to Athera Biotechnologies AB. Dr. Knuuti has been a consultant for GE Healthcare and AstraZeneca. Dr. Saraste has been a member of the Advisory Board for AstraZeneca; and has received speaker fees from AstraZeneca, Bayer, Novartis, and Abbott. 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 January 30, 2019.
- Revision received January 15, 2020.
- Accepted January 15, 2020.
- 2020 The Authors