CoChat
Sign Up
Cited by 56Nitric Oxide and Endothelin EffectsDiabetes Treatment and ManagementAtherosclerosis and Cardiovascular Diseases

Dipeptidyl peptidase-4 inhibitor, linagliptin, ameliorates endothelial dysfunction and atherogenesis in normoglycemic apolipoprotein-E deficient mice

Open access
Salim, Hotimah Masdan, Fukuda, Daiju, Higashikuni, Yasutomi, Tanaka, Kimie, Hirata, Yoichiro, Yagi, Shusuke, Soeki, Takeshi, Shimabukuro, Michio +1 more·2016·Vascular Pharmacology
DOI 10.1016/j.vph.2015.08.011
Open this paper in CoChat — free accountOpen PDF

Abstract

Background Dipeptidyl peptidase-4 (DPP-4) inhibitors have vasoprotective effects. This study investigated whether a recently approved DPP-4 inhibitor, linagliptin (Lina), suppresses atherogenesis in non-diabetic apolipoprotein-E deficient (ApoE(-/-)) mice, and examined its effects on endothelial function. Methods and results Lina (10mg/kg/day) was administered orally to ApoE(-/-) mice for 20 weeks. Lina reduced atherogenesis without alteration of metabolic parameters including blood glucose level compared with control (P<0.05). Results of immunohistochemical analyses and quantitative RT-PCR demonstrated that Lina significantly decreased inflammatory molecule expression and macrophage infiltration in the atherosclerotic aorta. Lina administration to ApoE(-/-) mice for 9 weeks ameliorated endothelium-dependent vasodilation compared with that in untreated mice. Plasma active glucagon-like peptide-1 (GLP-1) level was significantly higher in the treated group (P<0.05). Exendin-4 (Ex-4), a GLP-1 analog, ameliorated endothelium-dependent vasodilation impaired by palmitic acid (PA) in wild-type mouse aortic segments. Ex-4 promoted phosphorylation of eNOS(Ser1177) and Akt, both of which were abrogated by PA, in human umbilical vein endothelial cells. In addition, Lina administration to ApoE(-/-) mice decreased oxidative stress, as determined by urinary 8-OHdG secretion and NADPH oxidase subunit expression in the abdominal aorta. Conclusion Lina inhibited atherogenesis in non-diabetic ApoE(-/-) mice. Amelioration of endothelial dysfunction associated with a reduction of oxidative stress by GLP-1 contributes to the atheroprotective effects of Lina.

Integrity signals

Registry

Crossref · 10.1016/j.vph.2015.08.011

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Administration of linagliptin (10 mg/kg/day) to ApoE−/− mice decreased inflammatory molecule expression and macrophage infiltration in the atherosclerotic aorta.

    “Administration of linagliptin (10 mg/kg/day), a DPP-4 inhibitor, to ApoE−/− mice, an animal model of atherosclerosis, decreased inflammatory molecule expression and macrophage infiltration in the atherosclerotic aorta [65].”

    From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [65]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Salim, H. M., Fukuda, D., Higashikuni, Y., Tanaka, K., Hirata, Y., Yagi, S., Soeki, T., Shimabukuro, M., & Sata, M.
Affiliations
  • Tokushima University (JP)
  • The University of Tokyo (JP)
  • University of Tokyo Hospital (JP)
Corresponding author
Fukuda, Daiju
ORCID
Venue
Vascular Pharmacology
Publisher
Elsevier BV
Published
2016-04
Volume
79
Pages
16-23
ISSN
1537-1891 (ISSN-L)
DOI
10.1016/j.vph.2015.08.011
OpenAlex
W1122748781
Cited by
56
References
4
Citations by year
2026: 2 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 11 · 2017: 7 · 2016: 4 · 2015: 1
FWCI
5.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Vascular Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
Funders
Japan Society for the Promotion of Science (25860586, 22390159, 23591314, 25460369, 24659392, 25670390, 25293184, 25860843)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
linagliptin, DPP-4 inhibitors, atherogenesis, endothelial dysfunction, apolipoprotein E deficiency, glucagon-like peptide-1, exendin-4, oxidative stress, NADPH oxidase, eNOS phosphorylation, Akt signaling, macrophage infiltration, atherosclerosis, endothelium-dependent vasodilation, palmitic acid
MeSH terms
Linagliptin, Acetylcholine, Animals, Aorta, Thoracic, Apolipoproteins E, Blood Glucose, Dose-Response Relationship, Drug, Endothelium, Vascular, Humans, Male, Mice, Inbred C57BL, Organ Culture Techniques, Vasodilation, Mice, Knockout, Atherosclerosis, Mice, Dipeptidyl-Peptidase IV Inhibitors, Human Umbilical Vein Endothelial Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review