Related Experiment Video
Updated: May 2, 2026
In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1
Andreas Schober1, Maliheh Nazari-Jahantigh2, Yuanyuan Wei3
11] Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany. [2] Institute for Molecular Cardiovascular Research, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany. [3] DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany. [4].
Insights
Endothelial miR-126-5p prevents atherosclerosis by maintaining endothelial cell proliferation via Dlk1 suppression. Restoring miR-126-5p in mice limited lesion formation, offering a potential therapeutic strategy for this chronic inflammatory disease.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Inflammation Research
Background:
- Atherosclerosis is a chronic inflammatory arterial disease driven by hyperlipidemia and endothelial cell (EC) dysfunction.
- Disturbed laminar flow at specific arterial sites compromises EC function, promoting atherosclerotic lesion development.
- MicroRNAs (miRNAs) play critical roles in regulating cellular processes relevant to cardiovascular health.
Purpose of the Study:
- To investigate the role of endothelial miR-126-5p in maintaining EC proliferation and preventing atherosclerosis.
- To elucidate the molecular mechanism by which miR-126-5p regulates EC function under hyperlipidemic stress.
- To assess the therapeutic potential of miR-126-5p in mitigating atherosclerotic lesion formation.
Main Methods:
- Utilized Mir126(-/-) mice to study the effects of miR-126-5p deficiency on EC proliferation and atherosclerosis.
- Analyzed the expression of miR-126-5p, delta-like 1 homolog (Dlk1), and other relevant markers in ECs.
- Investigated EC recovery after denudation and atherosclerotic lesion formation at predilection and nonpredilection sites.
- Administered miR-126-5p to assess its therapeutic efficacy in a mouse model of atherosclerosis.
Main Results:
- Lack of endothelial miR-126-5p impaired EC proliferation and endothelial recovery after denudation by derepressing Dlk1.
- High miR-126-5p levels conferred a proliferative reserve in ECs at nonpredilection sites, compensating for hyperlipidemia.
- Disturbed flow downregulated miR-126-5p at predilection sites, abrogating EC proliferation and promoting atherosclerosis.
- miR-126-5p administration rescued EC proliferation and limited atherosclerotic lesion formation in mice.
Conclusions:
- Endothelial miR-126-5p is crucial for maintaining EC proliferative capacity and preventing atherosclerosis.
- miR-126-5p suppresses Dlk1, a key inhibitor of EC proliferation, thereby protecting against hyperlipidemia-induced damage.
- Targeting endothelial miR-126-5p represents a promising therapeutic strategy for atherosclerosis.
Abstract:
Atherosclerosis, a hyperlipidemia-induced chronic inflammatory process of the arterial wall, develops preferentially at sites where disturbed laminar flow compromises endothelial cell (EC) function. Here we show that endothelial miR-126-5p maintains a proliferative reserve in ECs through suppression of the Notch1 inhibitor delta-like 1 homolog (Dlk1) and thereby prevents atherosclerotic lesion formation. Endothelial recovery after denudation was impaired in Mir126(-/-) mice because lack of miR-126-5p, but not miR-126-3p, reduced EC proliferation by derepressing Dlk1. At nonpredilection sites, high miR-126-5p levels in endothelial cells confer a proliferative reserve that compensates for the antiproliferative effects of hyperlipidemia, such that atherosclerosis was exacerbated in Mir126(-/-) mice. In contrast, downregulation of miR-126-5p by disturbed flow abrogated EC proliferation at predilection sites in response to hyperlipidemic stress through upregulation of Dlk1 expression. Administration of miR-126-5p rescued EC proliferation at predilection sites and limited atherosclerosis, introducing a potential therapeutic approach.
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs