Evaluation of glucagon-like peptide-1 receptor expression in nondiabetic and diabetic atherosclerotic mice using PET tracer 68Ga-NODAGA-exendin-4

Mia Ståhle; Sanna Hellberg; Jenni Virta; Heidi Liljenbäck; Olli Metsälä; Xiang-Guo Li; Matti Jauhiainen; Pekka Saukko; Seppo Ylä-Herttuala; Pirjo Nuutila; Juhani Knuuti; Antti Saraste; Anne Roivainen

doi:10.1152/ajpendo.00465.2020

Evaluation of glucagon-like peptide-1 receptor expression in nondiabetic and diabetic atherosclerotic mice using PET tracer ⁶⁸Ga-NODAGA-exendin-4

Am J Physiol Endocrinol Metab. 2021 May 1;320(5):E989-E998. doi: 10.1152/ajpendo.00465.2020. Epub 2021 Apr 12.

Authors

Mia Ståhle¹, Sanna Hellberg¹, Jenni Virta¹, Heidi Liljenbäck^{1

2}, Olli Metsälä¹, Xiang-Guo Li^{1

3}, Matti Jauhiainen⁴, Pekka Saukko⁵, Seppo Ylä-Herttuala⁶, Pirjo Nuutila^{1

7}, Juhani Knuuti^{1

8}, Antti Saraste^{1

8

9}, Anne Roivainen^{1

2}

Affiliations

¹ Turku PET Centre, University of Turku, Turku, Finland.
² Turku Center for Disease Modeling, University of Turku, Turku, Finland.
³ Turku PET Centre, Åbo Akademi University, Turku, Finland.
⁴ Minerva Foundation Institute for Medical Research and Genomics and Biomarkers Unit, National Institute for Health and Welfare, Biomedicum, Helsinki, Finland.
⁵ Department of Pathology and Forensic Medicine, University of Turku, Turku, Finland.
⁶ A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
⁷ Department of Endocrinology, Turku University Hospital, Turku, Finland.
⁸ Turku PET Centre, Turku University Hospital, Turku, Finland.
⁹ Heart Center, Turku University Hospital, Turku, Finland.

PMID: 33843281
DOI: 10.1152/ajpendo.00465.2020

Abstract

Cardiovascular effects of glucagon-like peptide-1 receptor (GLP-1R) agonist therapies are potentially mediated by anti-inflammatory effects on atherosclerosis. Our study demonstrates that ⁶⁸Ga-NODAGA-exendin-4, a radioligand specifically targeting GLP-1R, detects GLP-1R expression in inflamed atherosclerotic lesions in nondiabetic and diabetic hypercholesterolemic mice. Immunofluorescence staining suggests that GLP-1R is primarily localized in M2 macrophages in lesions. This study describes a new potential tool that may have translational relevance for studies of pharmacological modification of GLP-1R signaling in atherosclerosis.

Keywords: atherosclerosis; glucagon-like peptide-1 receptor; inflammation; positron emission tomography.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetates / pharmacokinetics
Animals
Apolipoproteins B / genetics
Apolipoproteins B / metabolism
Atherosclerosis / complications
Atherosclerosis / diagnosis
Atherosclerosis / genetics
Atherosclerosis / metabolism*
Diabetes Mellitus, Experimental / complications
Diabetes Mellitus, Experimental / diagnosis
Diabetes Mellitus, Experimental / genetics
Diabetes Mellitus, Experimental / metabolism*
Exenatide / pharmacokinetics
Female
Gallium Radioisotopes / pharmacokinetics
Glucagon-Like Peptide-1 Receptor / agonists
Glucagon-Like Peptide-1 Receptor / genetics
Glucagon-Like Peptide-1 Receptor / metabolism*
Heterocyclic Compounds, 1-Ring / pharmacokinetics
Hypercholesterolemia / complications
Hypercholesterolemia / diagnosis
Hypercholesterolemia / genetics
Hypercholesterolemia / metabolism
Insulin-Like Growth Factor II / genetics
Insulin-Like Growth Factor II / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Positron-Emission Tomography / methods
Receptors, LDL / genetics
Receptors, LDL / metabolism

Substances

1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
Acetates
Apolipoproteins B
Gallium Radioisotopes
Glucagon-Like Peptide-1 Receptor
Heterocyclic Compounds, 1-Ring
Receptors, LDL
Insulin-Like Growth Factor II
Exenatide