Induction of microRNA-138 by pro-inflammatory cytokines causes endothelial cell dysfunction
| Autor: | Anagha Sen, Patrick Most, Karsten Peppel |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Biophysics 030204 cardiovascular system & hematology Biochemistry Nitric oxide Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Structural Biology Enos Internal medicine Genetics medicine Tumor necrosis factor-alpha Endothelial dysfunction Cytokine Molecular Biology 030304 developmental biology 0303 health sciences Endothelin-1 biology Angiotensin II Nitric Oxide Synthase Type III Cell Biology biology.organism_classification medicine.disease Endothelial stem cell Endocrinology chemistry Cancer research Endothelial nitric oxide synthase |
| Zdroj: | FEBS Letters. 588:906-914 |
| ISSN: | 0014-5793 |
| Popis: | Exposure to pro-inflammatory cytokines, such as Angiotensin II, endothelin-1 or TNF leads to endothelial dysfunction, characterized by the reduced production of nitric oxide via endothelial nitric oxide synthase (eNOS). We recently identified the Ca2+ binding protein S100A1 as an essential factor required for eNOS activity. Here we report that pro-inflammatory cytokines down-regulate expression of S100A1 in primary human microvascular endothelial cells (HMVECs) via induction of microRNA-138 (miR-138), in a manner that depends on the stabilization of HIF1-α. We show that loss of S100A1 in ECs reduces stimulus-induced NO production, which can be prevented by inhibition of miR-138. Our study suggests that targeting miR-138 might be beneficial for the treatment of cardiovascular disease. |
| Databáze: | OpenAIRE |
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