Therapeutic Antibody Against Phosphorylcholine Preserves Coronary Function and Attenuates Vascular 18F-FDG Uptake in Atherosclerotic Mice

Mia Ståhle; Johanna M U Silvola; Sanna Hellberg; Margreet de Vries; Paul H A Quax; Jeffrey Kroon; Petteri Rinne; Alwin de Jong; Heidi Liljenbäck; Nina Savisto; Anna Wickman; Erik S G Stroes; Seppo Ylä-Herttuala; Pekka Saukko; Tommy Abrahamsson; Knut Pettersson; Juhani Knuuti; Anne Roivainen; Antti Saraste

doi:10.1016/j.jacbts.2020.01.008

Therapeutic Antibody Against Phosphorylcholine Preserves Coronary Function and Attenuates Vascular ¹⁸F-FDG Uptake in Atherosclerotic Mice

JACC Basic Transl Sci. 2020 Mar 25;5(4):360-373. doi: 10.1016/j.jacbts.2020.01.008. eCollection 2020 Apr.

Authors

Mia Ståhle¹, Johanna M U Silvola¹, Sanna Hellberg¹, Margreet de Vries², Paul H A Quax², Jeffrey Kroon³, Petteri Rinne^{4

5}, Alwin de Jong², Heidi Liljenbäck^{1

5}, Nina Savisto¹, Anna Wickman⁶, Erik S G Stroes^{3

7}, Seppo Ylä-Herttuala⁸, Pekka Saukko⁹, Tommy Abrahamsson¹⁰, Knut Pettersson¹⁰, Juhani Knuuti^{1

11}, Anne Roivainen^{1

5}, Antti Saraste^{1

11

12

13}

Affiliations

¹ Turku PET Centre, University of Turku, Turku, Finland.
² Einthoven Laboratory for Experimental Vascular Medicine, Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
³ Department of Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, the Netherlands.
⁴ Research Center for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.
⁵ Turku Center for Disease Modeling, University of Turku, Turku, Finland.
⁶ i3tex AB, Gothenburg, Sweden.
⁷ Department of Vascular Medicine, Academic Medical Center, Amsterdam University Medical Center (UMC), Amsterdam, the Netherlands.
⁸ A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
⁹ Department of Pathology and Forensic Medicine, University of Turku, Turku, Finland.
¹⁰ Athera Biotechnologies AB, Stockholm, Sweden.
¹¹ Turku PET Centre, Turku University Hospital, Turku, Finland.
¹² Heart Center, Turku University Hospital, Turku, Finland.
¹³ Institute of Clinical Medicine, Turku University Hospital, Turku, Finland.

Abstract

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.

Keywords: 18F-FDG, 18F-fluorodeoxyglucose; 18F-fluorodeoxyglucose positron emission tomography; ANOVA, analysis of variance; ApoB, apolipoprotein-B; CFR, coronary flow reserve; HAEC, human aortic endothelial cell; ICAM, intracellular adhesion molecule; IL, interleukin; Ig, immunoglobulin; LDLR, low-density lipoprotein receptor; Lp(a), lipoprotein(a); NO, nitric oxide; OxLDL, oxidized low-density lipoprotein cholesterol; OxPLs, oxidized phospholipids; PC, phosphorylcholine; PC-mAb, human PC antibody; VCAM, vascular cell adhesion molecule; atherosclerosis; coronary flow reserve; inflammation; phosphorylcholine.