Cited by 156Diabetes Treatment and ManagementAtherosclerosis and Cardiovascular DiseasesDiabetes, Cardiovascular Risks, and Lipoproteins

DPP-4 (CD26) Inhibitor Alogliptin Inhibits Atherosclerosis in Diabetic Apolipoprotein E–Deficient Mice

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Ta, Nga N, Schuyler, Corinne A, Li, Yanchun, Lopes-Virella, Maria F, Huang, Yan·2011·Journal of Cardiovascular Pharmacology

Abstract

Dipeptidyl peptidase-4 (DPP-4 or CD26) inhibitors, a new class of antidiabetic compounds, are effective in the treatment of hyperglycemia. Because atherosclerosis-related cardiovascular diseases are the major complications of diabetes, it is important to determine the effect of DPP-4 inhibitors on atherosclerosis. In this study, nondiabetic and diabetic apolipoprotein E-deficient mice were treated with DPP-4 inhibitor alogliptin for 24 weeks, and atherosclerotic lesions in aortic origins were examined. Results showed that diabetes significantly increased atherosclerotic lesions, but alogliptin treatment reduced atherosclerotic lesions in diabetic mice. Metabolic studies showed that diabetes increased plasma glucose and that alogliptin treatment reduced glucose. Furthermore, immunohistochemistry study showed that diabetes increased interleukin-6 (IL-6) and IL-1β protein expression in atherosclerotic plaques, but alogliptin treatment attenuated diabetes-augmented IL-6 and IL-1β expression. In consistence with the observations from the mouse models, our in vitro studies showed that alogliptin-inhibited toll-like receptor 4 (TLR-4)-mediated upregulation of IL-6, IL-1β, and other proinflammatory cytokines by mononuclear cells. Taken together, our findings showed that alogliptin-inhibited atherosclerosis in diabetic apolipoprotein E-deficient mice and that the actions of alogliptin on both glucose and inflammation may contribute to the inhibition.

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Authors
Ta, N. N., Schuyler, C. A., Li, Y., Lopes-Virella, M. F., & Huang, Y.
Affiliations
Medical University of South Carolina (US)
Corresponding author
Huang, Yan
Venue
Journal of Cardiovascular Pharmacology
Published
2011-08
Volume
58
Issue
2
Pages
157-166
ISSN
0160-2446 (ISSN-L)
OpenAlex
W2059903872
Cited by
156
References
42
Citations by year
2025: 2 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 10 · 2019: 6 · 2018: 13 · 2017: 10 · 2016: 16 · 2015: 22 · 2014: 17 · 2013: 23 · 2012: 13
FWCI
13.89
Type
journal article
Language
en
Open access
Locations
  • Journal of Cardiovascular Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Dental and Craniofacial Research (R01DE016353, DE016353)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
alogliptin, DPP-4 inhibitors, atherosclerosis, diabetes mellitus, ApoE-deficient mice, interleukin-6, IL-1β, TLR4, inflammation, glucose, mononuclear cells, aortic atherosclerotic lesions
MeSH terms
Interleukin-6 Inhibitors, Animals, Apolipoproteins E, Blood Glucose, Cholesterol, Diabetes Mellitus, Experimental, Enzyme-Linked Immunosorbent Assay, Humans, Male, Piperidines, Triglycerides, Uracil, Mice, Knockout, Dipeptidyl Peptidase 4, U937 Cells, Atherosclerosis, Mice, Interleukin-1beta, Dipeptidyl-Peptidase IV Inhibitors, Real-Time Polymerase Chain Reaction

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