Epigenetic response of endothelial cells to different wall shear stress magnitudes: A report of new mechano-miRNAs

Sherif Rashad, Xiaobo Han, Khalid Saqr, Simon Andre Tupin, Makoto Ohta, Kuniyasu Niizuma, Teiji Tominaga

研究成果: Article査読

4 被引用数 (Scopus)

抄録

Endothelial cells (ECs) respond to flow stress via a variety of mechanisms, leading to various intracellular responses that can modulate the vessel wall and lead to diseases if the flow is disturbed. Mechano-microRNAs (miRNAs) are a subset of miRNAs in the ECs that are flow responsive. Mechano-miRNAs were shown to be related to atherosclerosis pathophysiology, and a number of them were identified as pathologic. Here, we exposed human carotid ECs to different wall shear stresses (WSS), high and low, and evaluated the response of miRNAs by microarray and quantitative polymerase chain reaction analysis. We discovered five new mechano-miRNAs that were not reported in that context previously to the best of our knowledge. Moreover, functional pathway analysis revealed that under low WSS conditions, several pathways regulating apoptosis are affected. In addition, KLF2 and KLF4, known atheroprotective genes, were downregulated under low WSS and upregulated under high WSS. KLF2 and VCAM1, both angiogenic, were upregulated under high WSS. NOS3, which is vascular protective, was also upregulated with higher WSS. On the contrary, ICAM-1 and E-selectin, both atherogenic and proinflammatory, were upregulated with high WSS. Collectively, the epigenetic landscape with the gene expression analysis reveals that low WSS is associated with a proapoptotic state, while high WSS is associated with a proliferative and proinflammatory state.

本文言語English
ページ(範囲)7827-7839
ページ数13
ジャーナルJournal of Cellular Physiology
235
11
DOI
出版ステータスPublished - 2020 11 1

ASJC Scopus subject areas

  • 生理学
  • 臨床生化学
  • 細胞生物学

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