scholarly journals Laminar Shear Stress Differentially Modulates Gene Expression of p120 Catenin, Kaiso Transcription Factor, and Vascular Endothelial Cadherin in Human Coronary Artery Endothelial Cells

2003 ◽  
Vol 279 (12) ◽  
pp. 11417-11424 ◽  
Author(s):  
Jyothisri Kondapalli ◽  
Annette S. Flozak ◽  
Maria Luiza C. Albuquerque
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Transcription Factor ◽  
Vascular Endothelial ◽  
Laminar Shear Stress ◽  
Human Coronary Artery ◽  
P120 Catenin ◽  
Vascular Endothelial Cadherin ◽  
Laminar Shear

Proteomic analysis of vascular endothelial cells in response to laminar shear stress

PROTEOMICS ◽  
2007 ◽  
Vol 7 (4) ◽  
pp. 588-596 ◽  
Author(s):  
Xiao-Li Wang ◽  
Alex Fu ◽  
Sreekumar Raghavakaimal ◽  
Hon-Chi Lee
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Proteomic Analysis ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Laminar Shear Stress ◽  
Laminar Shear

Abstract 442: Flow-Dependent Regulation of Angiopoietin-2

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Winfried Goettsch ◽  
Corina Gryczka ◽  
Thomas Korff ◽  
Evelyn Ernst ◽  
Claudia Goettsch ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Transcription Factor ◽  
High Flow ◽  
Low Flow ◽  
Laminar Shear Stress ◽  
Forkhead Box ◽  
Angiopoietin 2 ◽  
Laminar Shear

Background: Endothelial cells are constantly exposed to high or low shear stress in arteries and veins by the flowing blood. Angiopoietin-2 (Ang-2) is acting as a critical regulator of vessel maturation and endothelial cell quiescence. In this study, we determined the effect of low and high laminar shear stress on the expression and release of angiopoietin (Ang-)2 in human endothelial cells, studied the role of nitric oxide and protein kinases in this context, determined the impact of VEGF on Ang-2, studied the expression, activity and translocation of the forkhead box O transcription factor FOXO1 by low and high shear stress, and analyzed the vessel- and flow-dependent expression of Ang-2 in vivo . Methods and Results: Primary cultures of human umbilical vein endothelial cells (HUVEC) were subjected to laminar shear stress at different physiological levels of laminar shear stress of 1, 5, 10, 15, and 30 dyne/cm 2 in a cone-and-plate viscometer. Ang-2 mRNA, protein expression and release was upregulated by 24 h of low (1 dyne/cm 2 ), but downregulated by high flow (30 dyne/cm 2 ) in human endothelial cells. Increased endothelial NO synthase expression and NO formation was not affecting regulation of Ang-2 by low or high flow. Tie2 protein expression, but not Tie2 phosphorylation was induced by high flow. Furthermore, low and high flow increased VEGF-A expression. Inhibition of VEGFR-2 prevented upregulation of Ang-2 by low flow, but not downregulation of Ang-2 by high flow. Upregulation of Ang-2 by VEGF was reduced by application of high flow. Forkhead box O (FOXO) transcription factor FOXO1 has been shown to regulate Ang-2 expression in endothelial cells. FOXO1 binding activity was reduced by high flow. Nuclear localization of transcription factor FOXO1 was not changed by low flow, but reduced by high flow. In vivo , Ang-2 was higher expressed in veins compared to arteries. Arterial ligation augmented Ang-2 expression in distal arterial low flow areas. Conclusion: Our results support a VEGF-dependent induction of Ang-2 in low flow areas, and FOXO1-dependent downregulation of Ang-2 in high flow areas. These data suggest a new mechanism of flow-dependent regulation of vessel stability and differentiation.

Atheroprotective mechanisms of shear stress-regulated microRNAs

2012 ◽  
Vol 108 (10) ◽  
pp. 616-620 ◽  
Author(s):  
Reinier A. Boon ◽  
Eduard Hergenreider ◽  
Stefanie Dimmeler
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Cell Cycle Progression ◽  
Laminar Shear Stress ◽  
Cycle Progression ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Laminar Shear

SummaryMicroRNAs (miRs) are small non-coding RNAs that control gene expression by inhibiting translation or inducing degradation of targeted mRNA. miRs play a crucial role in vascular homeostasis but also during pathophysiological processes. Functionally active endothelial cells maintain homeostasis of the vasculature and protect against cardiovascular disease. The mechanical activation of endothelial cells by laminar shear stress provides a potent atheroprotective effect and reduces endothelial inflammation and cell cycle progression. Laminar shear stress induces profound changes in gene expression and recently was shown to regulate various miRs. The down-regulation of miR-92a by shear stress enhances the expression of the endothelial nitric oxide synthase, whereas the up-regulation of miR-19a contributes to the shear stress-induced inhibition of cell proliferation. In addition, members of the miR-23–27–24 cluster are increased and specifically miR-23b blocks cell cycle progression, whereas miR-27b was shown to reduce endothelial cell repulsive signals. Finally, increased miR-10 expression in atheroprotected regions reduced the inflammatory response of endothelial cells and increased endothelial miR-143/145 levels improved smooth muscle cells functions. Together, the regulation of miRs by shear stress contributes to the anti-inflammatory, cell cycle inhibitory and vasculoprotective effects in endothelial cells.

Shear-induced reactive nitrogen species inhibit mitochondrial respiratory complex activities in cultured vascular endothelial cells

2007 ◽  
Vol 292 (3) ◽  
pp. C1103-C1112 ◽  
Author(s):  
Zhaosheng Han ◽  
Yeong-Renn Chen ◽  
Charles I. Jones ◽  
Guruguhan Meenakshisundaram ◽  
Jay L. Zweier ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Reactive Nitrogen Species ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Nitrogen Species ◽  
Laminar Shear Stress ◽  
Steady Laminar Shear Stress ◽  
Laminar Shear ◽  
Steady Laminar

There is evidence that nitric oxide (NO), superoxide (O2•−), and their associated reactive nitrogen species (RNS) produced by vascular endothelial cells (ECs) in response to hemodynamic forces play a role in cell signaling. NO is known to impair mitochondrial respiration. We sought to determine whether exposure of human umbilical vein ECs (HUVECs) to steady laminar shear stress and the resultant NO production modulate electron transport chain (ETC) enzymatic activities. The activities of respiratory complexes I, II/III, and IV were dependent on the presence of serum and growth factor supplement in the medium. EC exposure to steady laminar shear stress (10 dyn/cm2) resulted in a gradual inhibition of each of the complexes starting as early as 5 min from the flow onset and lasting up to 16 h. Ramp flow resulted in inhibition of the complexes similar to that of step flow. When ECs were sheared in the presence of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME; 100 μM), the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO; 100 μM), or the peroxynitrite (ONOO−) scavenger uric acid (UA; 50 μM), the flow-inhibitory effect on mitochondrial complexes was attenuated. In particular, l-NAME and UA abolished the flow effect on complex IV. Increased tyrosine nitration was observed in the mitochondria of sheared ECs, and UA blocked the shear-induced nitrotyrosine staining. In summary, shear stress induces mitochondrial RNS formation that inhibits the electron flux of the ETC at multiple sites. This may be a critical mechanism by which shear stress modulates EC signaling and function.

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