scholarly journals Ion Channels in Endothelial Responses to Fluid Shear Stress

Physiology ◽  
2016 ◽  
Vol 31 (5) ◽  
pp. 359-369 ◽  
Author(s):  
Kristin A. Gerhold ◽  
Martin A. Schwartz
Keyword(s):  
Shear Stress ◽  
Ion Channels ◽  
Molecular Mechanisms ◽  
Fluid Shear Stress ◽  
Future Research ◽  
Fluid Shear ◽  
Environmental Cue ◽  
Vascular Physiology

Fluid shear stress is an important environmental cue that governs vascular physiology and pathology, but the molecular mechanisms that mediate endothelial responses to flow are only partially understood. Gating of ion channels by flow is one mechanism that may underlie many of the known responses. Here, we review the literature on endothelial ion channels whose activity is modulated by flow with an eye toward identifying important questions for future research.

scholarly journals Fluid shear stress stimulates phosphorylation-dependent nuclear export of HDAC5 and mediates expression of KLF2 and eNOS

Blood ◽  
2010 ◽  
Vol 115 (14) ◽  
pp. 2971-2979 ◽  
Author(s):  
Weiye Wang ◽  
Chang Hoon Ha ◽  
Bong Sook Jhun ◽  
Chelsea Wong ◽  
Mukesh K. Jain ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Nuclear Export ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Fluid Shear Stress ◽  
Inhibitory Effect ◽  
Fluid Shear ◽  
Enos Expression ◽  
Calcium Calmodulin Dependent

Abstract Fluid shear stress generated by steady laminar blood flow protects vessels from atherosclerosis. Krüppel-like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS) are fluid shear stress–responsive genes and key mediators in flow anti-inflammatory and antiatherosclerotic actions. However, the molecular mechanisms underlying flow induction of KLF2 and eNOS remain largely unknown. Here, we show a novel role of histone deacetylase 5 (HDAC5) in flow-mediated KLF2 and eNOS expression. We found for the first time that fluid shear stress stimulated HDAC5 phosphorylation and nuclear export in endothelial cells through a calcium/calmodulin-dependent pathway. Consequently, flow induced the dissociation of HDAC5 and myocyte enhancer factor-2 (MEF2) and enhanced MEF2 transcriptional activity, which leads to expression of KLF2 and eNOS. Adenoviral overexpression of a HDAC5 phosphorylation–defective mutant (Ser259/Ser498 were replaced by Ala259/Ala498, HDAC5-S/A), which shows resistance to flow-induced nuclear export, suppressed flow-mediated MEF2 transcriptional activity and expression of KLF2 and eNOS. Importantly, HDAC5-S/A attenuated the flow-inhibitory effect on monocyte adhesion to endothelial cells. Taken together, our results reveal that phosphorylation-dependent derepression of HDAC5 mediates flow-induced KLF2 and eNOS expression as well as flow anti-inflammation, and suggest that HDAC5 could be a potential therapeutic target for the prevention of atherosclerosis.

scholarly journals Epigenetic Changes During Mechanically Induced Osteogenic Lineage Commitment

2015 ◽  
Vol 137 (2) ◽  
Author(s):  
Julia C. Chen ◽  
Mardonn Chua ◽  
Raymond B. Bellon ◽  
Christopher R. Jacobs
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Methylation Status ◽  
Lineage Commitment ◽  
Fluid Shear ◽  
Osteogenic Lineage ◽  
Osteogenic Markers ◽  
Heterochromatin Structure

Osteogenic lineage commitment is often evaluated by analyzing gene expression. However, many genes are transiently expressed during differentiation. The availability of genes for expression is influenced by epigenetic state, which affects the heterochromatin structure. DNA methylation, a form of epigenetic regulation, is stable and heritable. Therefore, analyzing methylation status may be less temporally dependent and more informative for evaluating lineage commitment. Here we analyzed the effect of mechanical stimulation on osteogenic differentiation by applying fluid shear stress for 24 hr to osteocytes and then applying the osteocyte-conditioned medium (CM) to progenitor cells. We analyzed gene expression and changes in DNA methylation after 24 hr of exposure to the CM using quantitative real-time polymerase chain reaction and bisulfite sequencing. With fluid shear stress stimulation, methylation decreased for both adipogenic and osteogenic markers, which typically increases availability of genes for expression. After only 24 hr of exposure to CM, we also observed increases in expression of later osteogenic markers that are typically observed to increase after seven days or more with biochemical induction. However, we observed a decrease or no change in early osteogenic markers and decreases in adipogenic gene expression. Treatment of a demethylating agent produced an increase in all genes. The results indicate that fluid shear stress stimulation rapidly promotes the availability of genes for expression, but also specifically increases gene expression of later osteogenic markers.

Patterns of fluid shear stress determine atherosclerotic lesion size and vulnerability

2006 ◽  
Vol 45 (3) ◽  
pp. e51
Author(s):  
Caroline Cheng ◽  
Dennie Tempel ◽  
Luc van Damme ◽  
Rien van Haperen ◽  
Rob Krams ◽  
...  
Keyword(s):  
Shear Stress ◽  
Fluid Shear Stress ◽  
Atherosclerotic Lesion ◽  
Lesion Size ◽  
Fluid Shear

The rate of fluid shear stress is a potent regulator for the differentiation of mesenchymal stem cells

2019 ◽  
Vol 234 (9) ◽  
pp. 16312-16319 ◽  
Author(s):  
Danyang Yue ◽  
Mengxue Zhang ◽  
Juan Lu ◽  
Jin Zhou ◽  
Yuying Bai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Shear Stress ◽  
Mesenchymal Stem Cells ◽  
Fluid Shear Stress ◽  
Fluid Shear

scholarly journals Fluid shear stress induces osteoblast differentiation and arrests the cell cycle at the G0 phase via the ERK1/2 pathway

2017 ◽  
Vol 16 (6) ◽  
pp. 8699-8708 ◽  
Author(s):  
Liyin Yu ◽  
Xingfeng Ma ◽  
Junqin Sun ◽  
Jie Tong ◽  
Liang Shi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Shear Stress ◽  
Osteoblast Differentiation ◽  
Fluid Shear Stress ◽  
Fluid Shear ◽  
G0 Phase
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