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DPP-4 (CD26) Inhibitor Alogliptin Inhibits Atherosclerosis in Diabetic Apolipoprotein E–Deficient Mice
Open accessAbstract
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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Metadata
- 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)
- PMC
- PMC3155015
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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