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Induction of microRNA‐138 by pro‐inflammatory cytokines causes endothelial cell dysfunction
Author(s) -
Sen Anagha,
Most Patrick,
Peppel Karsten
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.01.033
Subject(s) - enos , nitric oxide , endothelial dysfunction , endothelial nitric oxide synthase , microrna , endothelin 1 , proinflammatory cytokine , inflammation , endothelial stem cell , tumor necrosis factor alpha , nitric oxide synthase , chemistry , medicine , microbiology and biotechnology , pharmacology , biology , biochemistry , in vitro , receptor , gene
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 Ca 2+ 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.