DPP-4 inhibition protects human umbilical vein endothelial cells from hypoxia-induced vascular barrier impairment
| Autor: | Yoshio Kobayashi, Masanori Hirose, Hiroyuki Takano, Naoko Hashimoto, Kento Ikuma, Hiroyuki Tadokoro, Yui Konno, Hiroshi Hasegawa |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Umbilical Veins Gene Expression 030204 cardiovascular system & hematology Biology Pharmacology Cell junction NF-κB Umbilical vein Adherens junction 03 medical and health sciences 0302 clinical medicine Endothelial cell Cell Adhesion medicine Dipeptidyl peptidase-4 Adherens junctions Humans Hypoglycemic Agents Hypoxia Cells Cultured Tube formation Dipeptidyl-Peptidase IV Inhibitors Tumor Necrosis Factor-alpha Cadherin lcsh:RM1-950 NF-kappa B Endothelial Cells Hypoxia (medical) Cadherins Immunohistochemistry Endothelial stem cell lcsh:Therapeutics. Pharmacology Intercellular Junctions 030104 developmental biology Cardiovascular Diseases Immunology Molecular Medicine Tumor necrosis factor alpha medicine.symptom Oligopeptides |
| Zdroj: | Journal of Pharmacological Sciences, Vol 135, Iss 1, Pp 29-36 (2017) |
| ISSN: | 1347-8613 |
| DOI: | 10.1016/j.jphs.2017.08.005 |
| Popis: | Dipeptidyl peptidase-4 (DPP-4) inhibitors are relatively new class of anti-diabetic drugs. Some protective effects of DPP-4 on cardiovascular disease have been described independently from glucose-lowering effect. However, the detailed mechanisms by which DPP-4 inhibitors exert on endothelial cells remain elusive. The purpose of this research was to determine the effects of DPP-4 inhibitor on endothelial barrier function. Human umbilical vein endothelial cells (HUVECs) were cultured and exposed to hypoxia in the presence or absence of Diprotin A, a DPP-4 inhibitor. Immunocytochemistry of vascular endothelial (VE-) cadherin showed that jagged VE-cadherin staining pattern induced by hypoxia was restored by treatment with Diprotin A. The increased level of cleaved β-catenin in response to hypoxia was significantly attenuated by Diprotin A, suggesting that DPP-4 inhibition protects endothelial adherens junctions from hypoxia. Subsequently, we found that Diprotin A inhibited hypoxia-induced translocation of NF-κB from cytoplasm to nucleus through decreasing TNF-α expression level. Furthermore, the tube formation assay showed that Diprotin A significantly restored hypoxia-induced decrease in number of tubes by HUVECs. These results suggest that DPP-4 inhibitior protects HUVECs from hypoxia-induced barrier impairment. |
| Databáze: | OpenAIRE |
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