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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: 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.

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

Endothelial cells seeded on the inner surface of silicone substrates.(A) Control conditions. ECs formed a confluent monolayer that has a cobblestone appearance. (B) After 7-h-exposure to WSS (10±10 dynes/cm2) and CS (4 ± 4%) at SPA = 0° and (C) SPA = -180°. ECs remained confluent but showed subtle morphological changes. Flow is from left to right; strain is perpendicular to flow.
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pone.0129952.g002: Endothelial cells seeded on the inner surface of silicone substrates.(A) Control conditions. ECs formed a confluent monolayer that has a cobblestone appearance. (B) After 7-h-exposure to WSS (10±10 dynes/cm2) and CS (4 ± 4%) at SPA = 0° and (C) SPA = -180°. ECs remained confluent but showed subtle morphological changes. Flow is from left to right; strain is perpendicular to flow.

Mentions: BAECs were exposed to WSS (10±10 dyn/cm2) and CS (4 ± 4) for 7 h in the hemodynamic simulator. The cells remained viable, with no signs of injury or desquamation, throughout the experiments at SPA = -180° and SPA = 0°. Staining with PI showed no increase in dead cells after exposure to shear stress and stretch (Data not shown). The cells showed morphological changes in response to WSS and CS, becoming partially elongated and aligned parallel to the direction of flow and perpendicular to the CS as shown in Fig 2. These results indicate that the device can be used to apply WSS and CS to endothelial cells without causing cell damage.


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

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

Endothelial cells seeded on the inner surface of silicone substrates.(A) Control conditions. ECs formed a confluent monolayer that has a cobblestone appearance. (B) After 7-h-exposure to WSS (10±10 dynes/cm2) and CS (4 ± 4%) at SPA = 0° and (C) SPA = -180°. ECs remained confluent but showed subtle morphological changes. Flow is from left to right; strain is perpendicular to flow.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492743&req=5

pone.0129952.g002: Endothelial cells seeded on the inner surface of silicone substrates.(A) Control conditions. ECs formed a confluent monolayer that has a cobblestone appearance. (B) After 7-h-exposure to WSS (10±10 dynes/cm2) and CS (4 ± 4%) at SPA = 0° and (C) SPA = -180°. ECs remained confluent but showed subtle morphological changes. Flow is from left to right; strain is perpendicular to flow.
Mentions: BAECs were exposed to WSS (10±10 dyn/cm2) and CS (4 ± 4) for 7 h in the hemodynamic simulator. The cells remained viable, with no signs of injury or desquamation, throughout the experiments at SPA = -180° and SPA = 0°. Staining with PI showed no increase in dead cells after exposure to shear stress and stretch (Data not shown). The cells showed morphological changes in response to WSS and CS, becoming partially elongated and aligned parallel to the direction of flow and perpendicular to the CS as shown in Fig 2. These results indicate that the device can be used to apply WSS and CS to endothelial cells without causing cell damage.

Bottom Line: 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.

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