Azilsartan protects against hyperglycemia-induced hyperpermeability of the blood-brain barrier
| Autor: | Wanxi Pan, Erliang Jin, Longfei Yao, Shaojun Chen, Hua Tang, Jing Han |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Angiotensin receptor Kruppel-Like Transcription Factors Bioengineering Pharmacology Blood–brain barrier Occludin Applied Microbiology and Biotechnology Neuroprotection Diabetes Mellitus Experimental Capillary Permeability azilsartan Mice Downregulation and upregulation Diabetes mellitus Azilsartan medicine Animals Oxadiazoles business.industry Antagonist General Medicine blood-brain barrier medicine.disease Neuroprotective Agents medicine.anatomical_structure klf2 Hyperglycemia diabetes mellitus cardiovascular system Cytokines Benzimidazoles business TP248.13-248.65 Research Article Research Paper medicine.drug Biotechnology |
| Zdroj: | Bioengineered, Vol 12, Iss 1, Pp 3621-3633 (2021) Bioengineered article-version (VoR) Version of Record |
| ISSN: | 2165-5987 2165-5979 |
| Popis: | Diabetes mellitus (DM) is a complex metabolic disease with significant neurological complications and is reported to be closely related to the blood-brain barrier (BBB) disruption. Azilsartan is an antagonist of the Angiotensin II receptor developed for the treatment of hypertension, and it has been recently reported to have neuroprotective effects. The present study aims to investigate the protective effect of Azilsartan against hyperglycemia-induced BBB disruption and its underlying mechanism. Male db/db mice were treated with Azilsartan (20 μg/day) for 10 consecutive days. Compared to the control group, increased BBB permeability, suppressed occludin expression, excessive release of inflammatory factors, and downregulation of krüppel-like factor 2 (KLF2) were observed in diabetic mice, all of which were dramatically reversed by Azilsartan treatment. In the in vitro experiments, elevated endothelial permeability and decreased expression of occludin and KLF2 were observed in high glucose-challenged endothelial cells, which were significantly alleviated by Azilsartan. Lastly, the silencing of KLF2 abolished the protective effects of Azilsartan against the high glucose-induced expression of occludin and endothelial monolayer permeability in bEnd.3 brain endothelial cells. Based on these observations, we concluded that Azilsartan protected against hyperglycemia-induced hyperpermeability of BBB via the KLF2/occludin axis. Graphical abstract |
| Databáze: | OpenAIRE |
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