A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

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




Julkaisun tekijät: Ståhle M, Hellberg S, Virta J, Liljenbäck H, Metsälä O, Li XG, Jauhiainen M, Saukko P, Ylä-Herttuala S, Nuutila P, Knuuti J, Saraste A, Roivainen A

Kustantaja: AMER PHYSIOLOGICAL SOC

Julkaisuvuosi: 2021

Journal: AJP - Endocrinology and Metabolism

Tietokannassa oleva lehden nimi: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

Lehden akronyymi: AM J PHYSIOL-ENDOC M

Volyymi: 320

Julkaisunumero: 5

Sivujen määrä: 10

ISSN: 0193-1849

eISSN: 1522-1555

DOI: http://dx.doi.org/10.1152/ajpendo.00465.2020


Tiivistelmä

Activation of glucagon-like peptide-1 receptor (GLP-1R) signaling attenuates development of atherosclerosis and vascular inflammation. However, the expression of GLP-1R in atherosclerotic arteries remains uncertain. We evaluated whether a positron emission tomography (PET) tracer 68Ga-NODAGA-exendin-4 enables detection and imaging of GLP-1R expression in the mouse atherosclerotic aorta. Hypercholesterolemic (LDLR-/-ApoB100/100), hypercholesterolemic, diabetic (IGF-II/LDLR-/-ApoB100/100), and healthy control (C57BL/6N) mice were used in the study. The uptake of 68Ga-NODAGA-exendin-4 in atherosclerotic lesions was studied by autoradiography of tissue sections followed by immunofluorescence evaluation of inflammatory and vascular cell markers and GLP-1R. A subset of mice was imaged with 68Ga-NODAGA-exendin-4 PET/computed tomography (CT). The aortas of both LDLR-/-ApoB100/100 and IGF-II/LDLR-/-ApoB100/100 mice contained prominent, macrophage-rich atherosclerotic lesions. Diabetic mice demonstrated hyperglycemia and glucose intolerance. We found that by autoradiography, 68Ga-NODAGA-exendin-4 uptake was focally increased in macrophage-rich lesion areas compared with corresponding healthy vessel wall (lesion-to-wall ratio 1.6 ± 0.10, P < 0.0001) in both nondiabetic and diabetic hypercholesterolemic mice. Preinjection of unlabeled exendin-4 peptide significantly reduced cellular uptake of 68Ga-NODAGA-exendin-4. Furthermore, PET/CT imaging showed 68Ga-NODAGAexendin-4 accumulation in the atherosclerotic aorta. Immunofluorescence stainings demonstrated colocalization of GLP-1R with macrophage-rich areas in atherosclerotic lesions. Tracer uptake was low in the healthy vessel wall of C57BL/6N mice coupled with negative GLP-1R staining. In conclusion, 68Ga-NODAGA-exendin-4 detects GLP-1R expression in atherosclerotic lesions in both nondiabetic and diabetic hypercholesterolemic mice. These results provide evidence that GLP-1R expression is mainly localized in macrophage-rich area in atherosclerotic lesions and may have implications for studies of pharmacological modification of GLP-1R signaling in atherosclerosis.


Last updated on 2021-23-09 at 13:22