MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases
Copyright policy )MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases
Significance This study demonstrates that hormone receptor RARα plays a vital role in the selective activation of proinflammatory and anti-inflammatory signaling to modulate the miR-10a/GATA6/VCAM-1 cascade in endothelial cells in response to proatherogenic oscillatory shear stress (OS) vs. atheroprotective pulsatile shear stress (PS). HDAC-3/5/7 and RXRα are induced by OS and PS to serve as mechanosensitive “repressors” and “enhancers,” respectively, to associate with RARα to modulate its binding to RA-responsive element (RARE) to switch miR-10a expression. Our findings provide insight into the relationship between two different epigenetic factors (HDACs and miRs) and hormone receptors (RARα and RXRα) in the regulation of endothelial functions and elucidate new mechanisms of hemodynamic-based pathophysiology of the atherosclerotic vascular wall.
- Taipei Medical University Taiwan
- University of California, San Diego United States
- National Tsing Hua University Taiwan
- Peking University China (People's Republic of)
- National Health Research Institutes Taiwan
Cells, Kruppel-Like Transcription Factors, Down-Regulation, Vascular Cell Adhesion Molecule-1, Cardiovascular, Small Interfering, Stress, shear stress, Histone Deacetylases, Medicinal and Biomolecular Chemistry, Vascular, GATA6 Transcription Factor, Genetics, 2.1 Biological and endogenous factors, Animals, Humans, Endothelium, Aetiology, RNA, Small Interfering, Aorta, Cells, Cultured, Cultured, Retinoid X Receptor alpha, microRNA, Retinoic Acid Receptor alpha, Endothelial Cells, hormone receptor, Mechanical, Atherosclerosis, endothelial cells, Rats, MicroRNAs, Chemical Sciences, histone deacetylase, RNA, RNA Interference, Endothelium, Vascular, Stress, Mechanical, Biotechnology, Signal Transduction
Cells, Kruppel-Like Transcription Factors, Down-Regulation, Vascular Cell Adhesion Molecule-1, Cardiovascular, Small Interfering, Stress, shear stress, Histone Deacetylases, Medicinal and Biomolecular Chemistry, Vascular, GATA6 Transcription Factor, Genetics, 2.1 Biological and endogenous factors, Animals, Humans, Endothelium, Aetiology, RNA, Small Interfering, Aorta, Cells, Cultured, Cultured, Retinoid X Receptor alpha, microRNA, Retinoic Acid Receptor alpha, Endothelial Cells, hormone receptor, Mechanical, Atherosclerosis, endothelial cells, Rats, MicroRNAs, Chemical Sciences, histone deacetylase, RNA, RNA Interference, Endothelium, Vascular, Stress, Mechanical, Biotechnology, Signal Transduction
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