Induction of microRNA-10a using retinoic acid receptor-α and retinoid x receptor-α agonists inhibits atherosclerotic lesion formation

Autor: Tung Lin Yang, Yi Hsuan Huang, Yu Tsung Shih, Wei Li Wang, Shu Yi Wei, Jeng Jiann Chiu, Li Jing Chen, Chih I. Lee, Chih-Cheng Wu, Ding Yu Lee
Rok vydání: 2017
Předmět:
0301 basic medicine
Apolipoprotein B
Coumaric Acids
Tetrahydronaphthalenes
medicine.drug_class
Mice
Knockout
ApoE
Aortic Diseases
Vascular Cell Adhesion Molecule-1
030204 cardiovascular system & hematology
Retinoid X receptor
Benzoates
Mechanotransduction
Cellular
03 medical and health sciences
0302 clinical medicine
Blood serum
GATA6 Transcription Factor
microRNA
medicine
Animals
Humans
Retinoid
Aorta
Cells
Cultured
Retinoid X Receptor alpha
biology
Cell adhesion molecule
Chemistry
Retinoic Acid Receptor alpha
Hemodynamics
Atherosclerosis
Plaque
Atherosclerotic
Rats
Up-Regulation
Endothelial stem cell
Retinoic acid receptor
Disease Models
Animal
MicroRNAs
030104 developmental biology
Regional Blood Flow
Cancer research
biology.protein
Stress
Mechanical
Cardiology and Cardiovascular Medicine
Zdroj: Atherosclerosis. 271
ISSN: 1879-1484
Popis: Background and aims MicroRNA (miR)-10a is a shear-regulated miR with the lowest expression in vascular endothelial cells (ECs) in athero-susceptible regions with oscillatory shear stress (OS). The aim of this study is to elucidate the relationship between EC miR-10a and atherosclerosis and develop a hemodynamics-based strategy for atherosclerosis treatment. Methods A combination of in vitro flow system and in vivo experimental animals was used to examine the functional roles of EC miR-10a and its clinical applications in atherosclerosis. Results En face staining showed that EC miR-10a is down-regulated in the inner curvature (OS region) of aortic arch in rats. Co-administration with retinoic acid receptor-α (RARα)- and retinoid X receptor-α (RXRα)-specific agonists rescued EC miR-10a expression in this OS region. These effects of OS and RARα/RXRα-specific agonists on EC miR-10a expression were confirmed by the in vitro flow system, and were modulated by the RARα-histone deacetylases complex, with the consequent modulation in the downstream GATA6/vascular cell adhesion molecule (VCAM)-1 signaling cascade. Animal studies showed that miR-10a levels are decreased in both aortic endothelium of atherosclerotic lesions and blood plasma from apolipoprotein E-deficient (ApoE−/−) mice. In vivo induction of EC miR-10a by administration of RARα/RXRα-specific agonists protects ApoE−/− mice from atherosclerosis through inhibition of GATA6/VCAM-1 signaling and inflammatory cell infiltration. Conclusions Our findings indicate that down-regulation of miR-10a in aortic endothelium and blood serum is associated with atherosclerosis, and miR-10a has potential to be developed as diagnostic molecule for atherosclerosis. Moreover, EC miR-10a induction by RARα/RXRα-specific agonists is a potential hemodynamics-based strategy for atherosclerosis treatment.
Databáze: OpenAIRE
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