Endothelial Dicer promotes atherosclerosis and vascular inflammation by miRNA-103-mediated suppression of KLF4

Petra Hartmann, Zhe Zhou, Lucia Natarelli, Yuanyuan Wei, Maliheh Nazari-Jahantigh, Mengyu Zhu, Jochen Grommes, Sabine Steffens, Christian Weber and Andreas Schober ()
Additional contact information
Petra Hartmann: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich
Zhe Zhou: Institute for Molecular Cardiovascular Research, RWTH Aachen University
Lucia Natarelli: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich
Yuanyuan Wei: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich
Maliheh Nazari-Jahantigh: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich
Mengyu Zhu: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich
Jochen Grommes: European Vascular Center Aachen-Maastricht, Medical University Maastricht
Sabine Steffens: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich
Christian Weber: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich
Andreas Schober: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: Abstract MicroRNAs regulate the maladaptation of endothelial cells (ECs) to naturally occurring disturbed blood flow at arterial bifurcations resulting in arterial inflammation and atherosclerosis in response to hyperlipidemic stress. Here, we show that reduced endothelial expression of the RNAse Dicer, which generates almost all mature miRNAs, decreases monocyte adhesion, endothelial C–X–C motif chemokine 1 (CXCL1) expression, atherosclerosis and the lesional macrophage content in apolipoprotein E knockout mice (Apoe−/−) after exposure to a high-fat diet. Endothelial Dicer deficiency reduces the expression of unstable miRNAs, such as miR-103, and promotes Krüppel-like factor 4 (KLF4)-dependent gene expression in murine atherosclerotic arteries. MiR-103 mediated suppression of KLF4 increases monocyte adhesion to ECs by enhancing nuclear factor-κB-dependent CXCL1 expression. Inhibiting the interaction between miR-103 and KLF4 reduces atherosclerosis, lesional macrophage accumulation and endothelial CXCL1 expression. Overall, our study suggests that Dicer promotes endothelial maladaptation and atherosclerosis in part by miR-103-mediated suppression of KLF4.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms10521 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10521

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10521

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().