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

Nature Communications
Petra HartmannAndreas Schober

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.

References

Aug 2, 2000·Proceedings of the National Academy of Sciences of the United States of America·L HajraM I Cybulsky
Oct 7, 2003·Nature Genetics·Emily BernsteinGregory J Hannon
Dec 23, 2004·The Journal of Biological Chemistry·Wei J YangGenshi Zhao
Jul 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Brian D HarfeClifford J Tabin
Oct 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Inger ØynebråtenGuttorm Haraldsen
Dec 13, 2005·The Journal of Clinical Investigation·Kush M ParmarGuillermo García-Cardeña
Oct 31, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Arnaud MonvoisinM Luisa Iruela-Arispe
Mar 7, 2007·The Journal of Biological Chemistry·Anne HamikMukesh K Jain
Mar 17, 2007·The Journal of Clinical Investigation·Chia-Lin TsouIsrael F Charo
Mar 24, 2007·Circulation Research·Yajaira SuárezWilliam C Sessa
Apr 3, 2007·Nature Genetics·Madhu S KumarTyler Jacks
Jun 2, 2007·Circulation Research·Angelika KuehbacherStefanie Dimmeler
Jul 4, 2007·The Journal of Experimental Medicine·Anne SchaeferPaul Greengard
Aug 8, 2008·Pacing and Clinical Electrophysiology : PACE·Hongwei JinFadi G Akar
Sep 10, 2008·Proceedings of the National Academy of Sciences of the United States of America·Yajaira SuárezWilliam C Sessa
Sep 24, 2008·Circulation·Paula A da Costa MartinsLeon J De Windt
Dec 3, 2008·Cell Metabolism·Ralph GareusManolis Pasparakis
Mar 26, 2009·BioTechniques·Gerard NuovoThomas Schmittgen
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lingfang ZengQingbo Xu
Dec 9, 2009·Biochemical and Biophysical Research Communications·Guadalupe VillarrealGuillermo García-Cardeña
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Xiaomei QinNanping Wang
Apr 10, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Sebastian AlbinssonWilliam C Sessa
Jun 17, 2010·The Journal of Biological Chemistry·Nils OhnesorgeMarc Schmidt
Jul 7, 2010·Cell·Graziano MartelloStefano Piccolo
Jul 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yun FangPeter F Davies
Mar 31, 2011·Nucleic Acids Research·Michael P GantierBryan R G Williams
Jun 10, 2011·Nature·Mirko TrajkovskiMarkus Stoffel
Jan 24, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Yun Fang, Peter F Davies
Mar 1, 2012·Thrombosis and Haemostasis·M Nazari-JahantighA Schober
Sep 11, 2012·Cell Metabolism·Marcelo A MoriC Ronald Kahn
Nov 20, 2012·The Journal of Clinical Investigation·Guangjin ZhouMukesh K Jain
Nov 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Xiaolu A CambronneRichard H Goodman

❮ Previous
Next ❯

Citations

Sep 14, 2016·Cellular and Molecular Life Sciences : CMLS·Farima ZahediAndreas Schober
Dec 23, 2016·Thrombosis and Haemostasis·Jie GaoDazhuo Shi
Apr 27, 2017·International Journal of Molecular Sciences·Jie ZhengShijun Lu
Mar 18, 2017·Current Opinion in Hematology·Eugene ChangMukesh K Jain
Mar 17, 2018·Current Opinion in Hematology·Carlos Fernández-Hernando, Yajaira Suárez
Oct 11, 2017·Nature Cell Biology·David GilotMarie-Dominique Galibert
Sep 19, 2017·Annals of Clinical Biochemistry·Eiji MunetsunaKoji Suzuki
Dec 3, 2016·Stroke; a Journal of Cerebral Circulation·Sandra DolzAida Lago
Mar 14, 2018·Circulation. Genomic and Precision Medicine·Jonathan P RehfussScott A Berceli
Jan 10, 2019·International Journal of Molecular Sciences·Zhuqing JinPappachan E Kolattukudy
Feb 15, 2019·Circulation Research·Sandeep KumarHanjoong Jo
Aug 26, 2016·Immunological Reviews·Theodore GurolQing Deng
Nov 27, 2019·Journal of Cellular and Molecular Medicine·Zhuona XiXiaolan Zhong
Jan 24, 2020·Clinical Science·Sneha RajuKathryn L Howe
Jul 13, 2016·Current Rheumatology Reports·Gregory R Sondag, Tariq M Haqqi
Jun 18, 2020·Nutrients·Saivageethi NuthikattuAmparo C Villablanca
Apr 4, 2017·Cardiovascular Therapeutics·Su-Jie JiaMing Zhao
Jan 23, 2017·Molecular and Cellular Biochemistry·Bing QinZhengqi Lu
Feb 21, 2018·Frontiers in Cardiovascular Medicine·David R SweetMukesh K Jain
Aug 1, 2020·Frontiers in Physiology·Linsey J F PetersDonato Santovito
Oct 8, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Quincy A HathawayJohn M Hollander
Jul 1, 2017·Oxidative Medicine and Cellular Longevity·Douglas F DluzenMichele K Evans
Jul 8, 2018·Nature Communications·Lucia NatarelliAndreas Schober
Jan 10, 2019·Molecular Therapy. Nucleic Acids·Zhenzhen ZhangChao Sun
Jun 8, 2018·JACC. Basic to Translational Science·Nina M PollakKonstantinos Drosatos
Dec 12, 2020·Pigment Cell & Melanoma Research·Arthur GautronDavid Gilot

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE53433
GSE53435

Methods Mentioned

BETA
PCR
transfection
antisense oligonucleotides
transfect
ELISA

Software Mentioned

GeneSpring GX
Ingenuity Pathway Analysis
GraphPad
StatMate
ImageJ
Leica LAS
StatMiner
Qbase PLUS
Multigauge
Prism

Related Concepts

Related Feeds

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.