Epigenetic response of endothelial cells to different wall shear stress magnitudes: A report of new mechano‐miRNAs. Issue 11 (8th January 2020)

• Record Type: Journal Article
• Authors: Rashad, Sherif; Han, Xiaobo; Saqr, Khalid; Tupin, Simon; Ohta, Makoto; Niizuma, Kuniyasu; Tominaga, Teiji
• Is Part Of: Journal of cellular physiology. Volume 235:Issue 11(2020:Nov.)
• Page Start: 7827
• Page End: 7839
• Publication Date: 2020-01-08
• Subjects: aneurysm rupture -- cerebral aneurysm -- endothelial cells -- mechano‐miRNAs -- microRNA -- wall shear stress; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29436
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: 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. Abstract : Endothelial cells sense flow via a variety of mechanisms. Here we present five novel mechano‐microRNAs that can shape the epigenetic landscape of endothelial cells toward a proapoptotic state under low wall shear stress (SS) and proliferative state under high wall SS. Our results can explain the pathology of aneurysmal growth and rupture.