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Effects of dipeptidyl peptidase 4 inhibition on inflammation in atherosclerosis : A 18F-fluorodeoxyglucose study of a mouse model of atherosclerosis and type 2 diabetes

Virta, Jenni ; Hellberg, Sanna ; Liljenbäck, Heidi ; Ståhle, Mia ; Silvola, Johanna M.U. ; Huusko, Jenni ; Söderström, Mirva ; Knuuti, Juhani ; Nuutila, Pirjo and Ylä-Herttuala, Seppo , et al. (2020) In Atherosclerosis 305. p.64-72
Abstract

Background and aims: Dipeptidyl peptidase 4 (DPP-4) inhibitors have anti-inflammatory and atheroprotective effects. We evaluated the effects of the DPP-4 inhibitor linagliptin on atherosclerotic plaque and hepatic inflammation using histology and 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG), a positron emission tomography tracer of inflammation, in a mouse model of hypercholesterolemia and type 2 diabetes. Methods: Igf2/Ldlr−/−Apob100/100 mice were fed a high-fat diet (HFD) for 8 weeks and then randomly allocated to receive HFD (n = 14), or HFD with added linagliptin (n = 15) for additional 12 weeks. Five mice fed a chow diet were studied as an additional control. At the end of the study,... (More)

Background and aims: Dipeptidyl peptidase 4 (DPP-4) inhibitors have anti-inflammatory and atheroprotective effects. We evaluated the effects of the DPP-4 inhibitor linagliptin on atherosclerotic plaque and hepatic inflammation using histology and 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG), a positron emission tomography tracer of inflammation, in a mouse model of hypercholesterolemia and type 2 diabetes. Methods: Igf2/Ldlr−/−Apob100/100 mice were fed a high-fat diet (HFD) for 8 weeks and then randomly allocated to receive HFD (n = 14), or HFD with added linagliptin (n = 15) for additional 12 weeks. Five mice fed a chow diet were studied as an additional control. At the end of the study, glucose tolerance, aortic and liver uptake of 18F-FDG, and histology were studied. Results: Mice in linagliptin and HFD groups had similar fasting glucose concentrations, but linagliptin improved glucose tolerance. Aortas of linagliptin and HFD groups showed advanced atherosclerotic plaques with no difference in the mean intima-to-media ratio or number of macrophages in the plaques. Autoradiography showed similar 18F-FDG uptake by atherosclerotic plaques in linagliptin and HFD groups (plaque-to-wall ratio: 1.7 ± 0.25 vs. 1.6 ± 0.21; p = 0.24). In the liver, linagliptin reduced the histologic inflammation score but had no effect on 18F-FDG uptake. Compared with chow diet, uptake of 18F-FDG was similar in the aorta, but higher in the liver after HFD. Conclusions: Linagliptin therapy improved glucose tolerance and reduced hepatic inflammation but had no effect on plaque burden or atherosclerotic inflammation, as determined by histology and 18F-FDG uptake, in atherosclerotic mice with type 2 diabetes.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
F-fluorodeoxyglucose, Atherosclerosis, Inflammation, Linagliptin, Type 2 diabetes
in
Atherosclerosis
volume
305
pages
9 pages
publisher
Elsevier
external identifiers
  • pmid:32386751
  • scopus:85088675224
ISSN
0021-9150
DOI
10.1016/j.atherosclerosis.2020.03.029
language
English
LU publication?
yes
id
2e732580-51f7-42ba-a747-d485ad272cf1
date added to LUP
2021-01-11 14:51:06
date last changed
2024-05-30 03:19:04
@article{2e732580-51f7-42ba-a747-d485ad272cf1,
  abstract     = {{<p>Background and aims: Dipeptidyl peptidase 4 (DPP-4) inhibitors have anti-inflammatory and atheroprotective effects. We evaluated the effects of the DPP-4 inhibitor linagliptin on atherosclerotic plaque and hepatic inflammation using histology and 2-deoxy-2-[<sup>18</sup>F]-fluoro-D-glucose (<sup>18</sup>F-FDG), a positron emission tomography tracer of inflammation, in a mouse model of hypercholesterolemia and type 2 diabetes. Methods: Igf2/Ldlr<sup>−/−</sup>Apob<sup>100/100</sup> mice were fed a high-fat diet (HFD) for 8 weeks and then randomly allocated to receive HFD (n = 14), or HFD with added linagliptin (n = 15) for additional 12 weeks. Five mice fed a chow diet were studied as an additional control. At the end of the study, glucose tolerance, aortic and liver uptake of <sup>18</sup>F-FDG, and histology were studied. Results: Mice in linagliptin and HFD groups had similar fasting glucose concentrations, but linagliptin improved glucose tolerance. Aortas of linagliptin and HFD groups showed advanced atherosclerotic plaques with no difference in the mean intima-to-media ratio or number of macrophages in the plaques. Autoradiography showed similar <sup>18</sup>F-FDG uptake by atherosclerotic plaques in linagliptin and HFD groups (plaque-to-wall ratio: 1.7 ± 0.25 vs. 1.6 ± 0.21; p = 0.24). In the liver, linagliptin reduced the histologic inflammation score but had no effect on <sup>18</sup>F-FDG uptake. Compared with chow diet, uptake of <sup>18</sup>F-FDG was similar in the aorta, but higher in the liver after HFD. Conclusions: Linagliptin therapy improved glucose tolerance and reduced hepatic inflammation but had no effect on plaque burden or atherosclerotic inflammation, as determined by histology and <sup>18</sup>F-FDG uptake, in atherosclerotic mice with type 2 diabetes.</p>}},
  author       = {{Virta, Jenni and Hellberg, Sanna and Liljenbäck, Heidi and Ståhle, Mia and Silvola, Johanna M.U. and Huusko, Jenni and Söderström, Mirva and Knuuti, Juhani and Nuutila, Pirjo and Ylä-Herttuala, Seppo and Gomez, Maria F. and Roivainen, Anne and Saraste, Antti}},
  issn         = {{0021-9150}},
  keywords     = {{F-fluorodeoxyglucose; Atherosclerosis; Inflammation; Linagliptin; Type 2 diabetes}},
  language     = {{eng}},
  pages        = {{64--72}},
  publisher    = {{Elsevier}},
  series       = {{Atherosclerosis}},
  title        = {{Effects of dipeptidyl peptidase 4 inhibition on inflammation in atherosclerosis : A <sup>18</sup>F-fluorodeoxyglucose study of a mouse model of atherosclerosis and type 2 diabetes}},
  url          = {{http://dx.doi.org/10.1016/j.atherosclerosis.2020.03.029}},
  doi          = {{10.1016/j.atherosclerosis.2020.03.029}},
  volume       = {{305}},
  year         = {{2020}},
}