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FEBS Lett. 2014 Mar 18;588(6):906-14. doi: 10.1016/j.febslet.2014.01.033. Epub 2014 Jan 31.

Induction of microRNA-138 by pro-inflammatory cytokines causes endothelial cell dysfunction.

Author information

1
Center for Translational Medicine, Jefferson Medical College, Philadelphia, PA, USA.
2
Center for Translational Medicine, Jefferson Medical College, Philadelphia, PA, USA; Laboratory for Molecular and Translational Cardiology, Department of Internal Medicine III, University of Heidelberg, INF 350, 69120 Heidelberg, Germany; DZHK (German Center for Cardiovascular Research), Partner site Heidelberg/Mannheim, Heidelberg University Hospital, INF 410, 69120 Heidelberg, Germany.
3
Center for Translational Medicine, Jefferson Medical College, Philadelphia, PA, USA. Electronic address: Karsten.Peppel@Jefferson.edu.

Abstract

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.

KEYWORDS:

Angiotensin II; Cytokine; Endothelial dysfunction; Endothelial nitric oxide synthase; Endothelin-1; Tumor necrosis factor-alpha

PMID:
24486907
PMCID:
PMC3975049
DOI:
10.1016/j.febslet.2014.01.033
[Indexed for MEDLINE]
Free PMC Article

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