{"doi":"10.1016/j.vph.2017.03.003","title":"Teneligliptin, a dipeptidyl peptidase-4 inhibitor, attenuated pro-inflammatory phenotype of perivascular adipose tissue and inhibited atherogenesis in normoglycemic apolipoprotein-E-deficient mice","abstract":null,"journal":"Vascular Pharmacology","year":2017,"id":590205,"datarank":2.1133097314088234,"base_score":3.9512437185814275,"endowment":3.9512437185814275,"self_citation_contribution":0.5926865577872142,"citation_network_contribution":1.520623173621609,"self_endowment_contribution":0.5926865577872142,"citer_contribution":1.520623173621609,"corpus_percentile":null,"corpus_rank":null,"citation_count":51,"citer_count":49,"citers_with_citation_signal":45,"citers_with_endowment":45,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1510104,"name":"Daiju Fukuda","orcid":null,"position":1,"is_corresponding":false},{"id":1410652,"name":"Yasutomi Higashikuni","orcid":"0000-0002-2232-567X","position":2,"is_corresponding":false},{"id":1510105,"name":"Kimie Tanaka","orcid":null,"position":3,"is_corresponding":false},{"id":1510106,"name":"Yoichiro Hirata","orcid":null,"position":4,"is_corresponding":false},{"id":1510107,"name":"Shusuke Yagi","orcid":null,"position":5,"is_corresponding":false},{"id":1510108,"name":"Takeshi Soeki","orcid":null,"position":6,"is_corresponding":false},{"id":1312719,"name":"Michio Shimabukuro","orcid":"0000-0001-7835-7665","position":7,"is_corresponding":false},{"id":704956,"name":"Masataka Sata","orcid":"0000-0002-8036-7501","position":8,"is_corresponding":false},{"id":1510103,"name":"Hotimah Masdan Salim","orcid":"0000-0002-0156-5287","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Teneligliptin, a dipeptidyl peptidase-4 inhibitor, attenuated pro-inflammatory phenotype of perivascular adipose tissue and inhibited atherogenesis in normoglycemic apolipoprotein-E-deficient mice","abstract":"<h4>Background</h4>Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether teneligliptin alters the pro-inflammatory phenotype of perivascular adipose tissue (PVAT) and inhibits atherogenesis.<h4>Methods and results</h4>Teneligliptin (60mg/kg/day) was administered orally to apolipoprotein-E-deficient (ApoE<sup>-/-</sup>) mice for 20weeks. Teneligliptin significantly inhibited the development of atherosclerosis in the aortic arch compared with vehicle (P<0.05), without alteration of blood glucose level or blood pressure. Histological analyses demonstrated that teneligliptin decreased lipid deposition and MCP-1 expression (P<0.05, respectively), and tended to decrease macrophage accumulation in atherosclerotic plaques. The results of quantitative RT-PCR analysis demonstrated that teneligliptin reduced the expression of inflammatory molecules such as TNF-α and MCP-1 in the abdominal aorta. Furthermore, teneligliptin reduced the expression of a macrophage marker and Nox-4, a major NADPH oxidase subunit in adipocytes, in PVAT around the aortic arch. Administration of teneligliptin for 8weeks ameliorated endothelium-dependent vasodilation and reduced oxidative stress as determined by urinary 8-OHdG excretion (P<0.05) compared with vehicle. In vitro experiments demonstrated that exendin-4 (Ex-4), a GLP-1 analog, decreased the expression of inflammatory molecules in RAW264.7 cells. Also, Ex-4 decreased Nox4 expression in 3T3-L1 adipocytes.<h4>Conclusion</h4>Teneligliptin inhibited atherogenesis with attenuation of the inflammatory phenotype in PVAT. A GLP-1 analog suppressed pro-inflammatory activation of macrophages and adipocytes. Suppression of the pro-inflammatory phenotype of PVAT might contribute, at least partially, to the cardioprotective effects of teneligliptin.","is_dataset_classified":null,"base_score":3.9512437185814275,"endowment":3.9512437185814275,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28347868","pmcid":null,"openalex_id":"https://openalex.org/W2602708407","authors":[],"funders":[{"funder_name":"Japan Society for the Promotion of Science","grant_id":"15K09133","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"22390159","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"23591314","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"24659392","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"25293184","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"25460369","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"25670390","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"25860586","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"25860843","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"26461141","title":null},{"funder_name":"Ministry of Education, Culture, Sports, Science and Technology","grant_id":"21117007","title":null}],"total_grants":11,"fwci":5.3887,"citation_percentile":0.96767619,"influential_citations":0,"citation_trend":[{"year":2017,"count":3},{"year":2018,"count":7},{"year":2019,"count":5},{"year":2020,"count":15},{"year":2021,"count":6},{"year":2022,"count":3},{"year":2023,"count":5},{"year":2024,"count":1},{"year":2025,"count":2},{"year":2026,"count":4}],"oa_status":"closed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S1537189116303184?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1537189116303184?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.vph.2017.03.003","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28347868","host_type":"repository"}],"fields_of_study":["Cardiovascular Disease and Adiposity","Cardiovascular Function and Risk Factors","Omental and Epiploic Conditions","3T3-L1 Cells","Adipose Tissue","Animals","Anti-Inflammatory Agents","Aorta","Aortic Diseases","Apolipoproteins E","Atherosclerosis","Cytokines","Dipeptidyl Peptidase 4","Dipeptidyl-Peptidase IV Inhibitors","Disease Models, Animal","Exenatide","Female","Genetic Predisposition to Disease","Incretins","Inflammation Mediators","Macrophage Activation","Macrophages","Male","Mice","Mice, Inbred C57BL","Mice, Knockout","Oxidative Stress","Peptides","Phenotype","Plaque, Atherosclerotic","Pyrazoles","RAW 264.7 Cells","Signal Transduction","Thiazolidines","Time Factors","Vasodilation","Venoms"],"mesh_terms":["RAW 264.7 Cells","Exenatide","Adipose Tissue","Animals","Anti-Inflammatory Agents","Aorta","Aortic Diseases","Apolipoproteins E","Disease Models, Animal","Female","Macrophage Activation","Macrophages","Male","Mice, Inbred C57BL","Peptides","Phenotype","Pyrazoles","Time Factors","Vasodilation","Venoms","Signal Transduction","Cytokines","Mice, Knockout","Oxidative Stress","Dipeptidyl Peptidase 4","Inflammation Mediators","Genetic Predisposition to Disease","3T3-L1 Cells","Atherosclerosis","Mice","Thiazolidines","Incretins","Dipeptidyl-Peptidase IV Inhibitors","Plaque, Atherosclerotic"],"keywords":["Endocrinology","Adipose tissue","Internal medicine","Dipeptidyl peptidase-4 inhibitor","Chemistry","NADPH oxidase","Apolipoprotein E","Apolipoprotein B","Oxidative stress","Pharmacology","Medicine","Type 2 diabetes","Diabetes mellitus","Cholesterol","Atherosclerosis","Inflammation","Endothelial function","Dpp-4 Inhibitors","Perivascular Adipose Tissue"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-24T14:28:19.526076Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}