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The Interaction between Fluid Wall Shear Stress and Solid Circumferential Strain Affects Endothelial Gene Expression.

Amaya R, Pierides A, Tarbell JM - PLoS ONE (2015)

Bottom Line: This study used a novel bioreactor to investigate the cellular response of bovine aortic endothelial cells (BAECS) exposed to a combination of pulsatile WSS and CS at SPA=0 or SPA=-180.Using a PCR array of 42 genes, we determined that BAECS exposed to non-reversing sinusoidal WSS (10±10 dyne/cm2) and CS (4 ± 4%) over a 7 hour testing period displayed 17 genes that were up regulated by SPA = -180 °, most of them pro-atherogenic, including NFκB and other NFκB target genes.These data suggest that asynchronous hemodynamics (SPA=-180 °) can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA may be an important parameter characterizing arterial susceptibility to disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, City College of New York, City University of New York, New York, New York, 10031, United States of America.

ABSTRACT
Endothelial cells lining the walls of blood vessels are exposed simultaneously to wall shear stress (WSS) and circumferential stress (CS) that can be characterized by the temporal phase angle between WSS and CS (stress phase angle - SPA). Regions of the circulation with highly asynchronous hemodynamics (SPA close to -180°) such as coronary arteries are associated with the development of pathological conditions such as atherosclerosis and intimal hyperplasia whereas more synchronous regions (SPA closer to 0°) are spared of disease. The present study evaluates endothelial cell gene expression of 42 atherosclerosis-related genes under asynchronous hemodynamics (SPA=-180 °) and synchronous hemodynamics (SPA=0 °). This study used a novel bioreactor to investigate the cellular response of bovine aortic endothelial cells (BAECS) exposed to a combination of pulsatile WSS and CS at SPA=0 or SPA=-180. Using a PCR array of 42 genes, we determined that BAECS exposed to non-reversing sinusoidal WSS (10±10 dyne/cm2) and CS (4 ± 4%) over a 7 hour testing period displayed 17 genes that were up regulated by SPA = -180 °, most of them pro-atherogenic, including NFκB and other NFκB target genes. The up regulation of NFκB p50/p105 and p65 by SPA =-180° was confirmed by Western blots and immunofluorescence staining demonstrating the nuclear translocation of NFκB p50/p105 and p65. These data suggest that asynchronous hemodynamics (SPA=-180 °) can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA may be an important parameter characterizing arterial susceptibility to disease.

No MeSH data available.


Related in: MedlinePlus

Hemodynamic influences on gene expression.Asynchronous hemodynamic conditions significantly increased the levels of mRNA of the apoptosis factor BCL2. Synchronous hemodynamics significantly reduced BAX and FAS mRNA levels (A). Asynchronous hemodynamics significantly increased the mRNA levels of PPARG, CCL5 and NFκB relative to synchronous conditions (B). Synchronous hemodynamics significantly decreased the mRNA levels of SOD1 compared to controls and SPA = −180° (C). Asynchronous hemodynamics significantly increased the mRNA levels of BMP4, GPC1, TGFb1 and VEGF compared to SPA 0°. Synchronous hemodynamic conditions decreased the gene expression of ANGTP2 and PRDX2 compared to control (D). (n = 11).
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pone.0129952.g004: Hemodynamic influences on gene expression.Asynchronous hemodynamic conditions significantly increased the levels of mRNA of the apoptosis factor BCL2. Synchronous hemodynamics significantly reduced BAX and FAS mRNA levels (A). Asynchronous hemodynamics significantly increased the mRNA levels of PPARG, CCL5 and NFκB relative to synchronous conditions (B). Synchronous hemodynamics significantly decreased the mRNA levels of SOD1 compared to controls and SPA = −180° (C). Asynchronous hemodynamics significantly increased the mRNA levels of BMP4, GPC1, TGFb1 and VEGF compared to SPA 0°. Synchronous hemodynamic conditions decreased the gene expression of ANGTP2 and PRDX2 compared to control (D). (n = 11).

Mentions: We analyzed the gene expression of apoptosis regulating proteins: the BCL2-associated X (BAX), B-cell lymphoma 2 (BCL2), Tumor Necrosis Factor-Alpha-Induced Protein-3 (TNFAIP-3 / A20), and Apoptosis Stimulating Factor (Fas) as shown in Fig 4A. Synchronous condition decreased BAX (~1.7-fold) mRNA levels compared with control. Asynchronous conditions very significantly increased BCL2 mRNA levels by 3.2-fold compared with static control and by 4.0-fold compared to synchronous hemodynamic conditions. Synchronous conditions significantly reduced FAS mRNA levels (~2.5-fold) compared with static control and asynchronous conditions.


The Interaction between Fluid Wall Shear Stress and Solid Circumferential Strain Affects Endothelial Gene Expression.

Amaya R, Pierides A, Tarbell JM - PLoS ONE (2015)

Hemodynamic influences on gene expression.Asynchronous hemodynamic conditions significantly increased the levels of mRNA of the apoptosis factor BCL2. Synchronous hemodynamics significantly reduced BAX and FAS mRNA levels (A). Asynchronous hemodynamics significantly increased the mRNA levels of PPARG, CCL5 and NFκB relative to synchronous conditions (B). Synchronous hemodynamics significantly decreased the mRNA levels of SOD1 compared to controls and SPA = −180° (C). Asynchronous hemodynamics significantly increased the mRNA levels of BMP4, GPC1, TGFb1 and VEGF compared to SPA 0°. Synchronous hemodynamic conditions decreased the gene expression of ANGTP2 and PRDX2 compared to control (D). (n = 11).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4492743&req=5

pone.0129952.g004: Hemodynamic influences on gene expression.Asynchronous hemodynamic conditions significantly increased the levels of mRNA of the apoptosis factor BCL2. Synchronous hemodynamics significantly reduced BAX and FAS mRNA levels (A). Asynchronous hemodynamics significantly increased the mRNA levels of PPARG, CCL5 and NFκB relative to synchronous conditions (B). Synchronous hemodynamics significantly decreased the mRNA levels of SOD1 compared to controls and SPA = −180° (C). Asynchronous hemodynamics significantly increased the mRNA levels of BMP4, GPC1, TGFb1 and VEGF compared to SPA 0°. Synchronous hemodynamic conditions decreased the gene expression of ANGTP2 and PRDX2 compared to control (D). (n = 11).
Mentions: We analyzed the gene expression of apoptosis regulating proteins: the BCL2-associated X (BAX), B-cell lymphoma 2 (BCL2), Tumor Necrosis Factor-Alpha-Induced Protein-3 (TNFAIP-3 / A20), and Apoptosis Stimulating Factor (Fas) as shown in Fig 4A. Synchronous condition decreased BAX (~1.7-fold) mRNA levels compared with control. Asynchronous conditions very significantly increased BCL2 mRNA levels by 3.2-fold compared with static control and by 4.0-fold compared to synchronous hemodynamic conditions. Synchronous conditions significantly reduced FAS mRNA levels (~2.5-fold) compared with static control and asynchronous conditions.

Bottom Line: This study used a novel bioreactor to investigate the cellular response of bovine aortic endothelial cells (BAECS) exposed to a combination of pulsatile WSS and CS at SPA=0 or SPA=-180.Using a PCR array of 42 genes, we determined that BAECS exposed to non-reversing sinusoidal WSS (10±10 dyne/cm2) and CS (4 ± 4%) over a 7 hour testing period displayed 17 genes that were up regulated by SPA = -180 °, most of them pro-atherogenic, including NFκB and other NFκB target genes.These data suggest that asynchronous hemodynamics (SPA=-180 °) can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA may be an important parameter characterizing arterial susceptibility to disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, City College of New York, City University of New York, New York, New York, 10031, United States of America.

ABSTRACT
Endothelial cells lining the walls of blood vessels are exposed simultaneously to wall shear stress (WSS) and circumferential stress (CS) that can be characterized by the temporal phase angle between WSS and CS (stress phase angle - SPA). Regions of the circulation with highly asynchronous hemodynamics (SPA close to -180°) such as coronary arteries are associated with the development of pathological conditions such as atherosclerosis and intimal hyperplasia whereas more synchronous regions (SPA closer to 0°) are spared of disease. The present study evaluates endothelial cell gene expression of 42 atherosclerosis-related genes under asynchronous hemodynamics (SPA=-180 °) and synchronous hemodynamics (SPA=0 °). This study used a novel bioreactor to investigate the cellular response of bovine aortic endothelial cells (BAECS) exposed to a combination of pulsatile WSS and CS at SPA=0 or SPA=-180. Using a PCR array of 42 genes, we determined that BAECS exposed to non-reversing sinusoidal WSS (10±10 dyne/cm2) and CS (4 ± 4%) over a 7 hour testing period displayed 17 genes that were up regulated by SPA = -180 °, most of them pro-atherogenic, including NFκB and other NFκB target genes. The up regulation of NFκB p50/p105 and p65 by SPA =-180° was confirmed by Western blots and immunofluorescence staining demonstrating the nuclear translocation of NFκB p50/p105 and p65. These data suggest that asynchronous hemodynamics (SPA=-180 °) can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA may be an important parameter characterizing arterial susceptibility to disease.

No MeSH data available.


Related in: MedlinePlus