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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

Hemodynamic influences on gene expression.Asynchronous hemodynamic conditions significantly increased the expression of the adhesion molecules CDH5 and VCAM-1 (B). Asynchronous hemodynamic conditions significantly increased EPCR and SCD1 mRNA levels (C). Asynchronous hemodynamic conditions significantly increased the mRNA levels of transcription regulators OLR-1, ADFP, and SCARB1 (D) **p < 0.05, * p<0.1 indicate significant differences for SPA 0° with respect to control or SPA -180° with respect to control. An overbar indicates pairwise significant difference between SPA 0° and SPA -180°. (n = 11)
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pone.0129952.g003: Hemodynamic influences on gene expression.Asynchronous hemodynamic conditions significantly increased the expression of the adhesion molecules CDH5 and VCAM-1 (B). Asynchronous hemodynamic conditions significantly increased EPCR and SCD1 mRNA levels (C). Asynchronous hemodynamic conditions significantly increased the mRNA levels of transcription regulators OLR-1, ADFP, and SCARB1 (D) **p < 0.05, * p<0.1 indicate significant differences for SPA 0° with respect to control or SPA -180° with respect to control. An overbar indicates pairwise significant difference between SPA 0° and SPA -180°. (n = 11)

Mentions: We analyzed the regulation of mRNA levels for vasoactive genes endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1) and cyclooxygenase-2 (COX-2). WSS and CS induced 2.3 and 3.3 fold increase in eNOS mRNA levels for SPA = 0° and SPA = -180°, respectively, compared to static control, indicating that BAECs were responsive to WSS and CS (Fig 3A). Asynchronous hemodynamics increased ET-1 mRNA levels ~1.55-fold relative to static controls. Synchronous hemodynamics increased COX-2 mRNA levels ~3.55-fold relative to static control. There were no significant differences between synchronous and asynchronous conditions for any of these genes. WSS and CS showed a significant difference from static controls in ET-1 mRNA levels for SPA = -180° but not SPA = 0°. WSS and CS induced 3.3 and 2.2-fold increases in COX-2 mRNA levels for SPA = 0° and SPA = -180° respectively. Only SPA = 0° induced a significant increase in COX-2 mRNA levels compared with static controls.


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 expression of the adhesion molecules CDH5 and VCAM-1 (B). Asynchronous hemodynamic conditions significantly increased EPCR and SCD1 mRNA levels (C). Asynchronous hemodynamic conditions significantly increased the mRNA levels of transcription regulators OLR-1, ADFP, and SCARB1 (D) **p < 0.05, * p<0.1 indicate significant differences for SPA 0° with respect to control or SPA -180° with respect to control. An overbar indicates pairwise significant difference between SPA 0° and SPA -180°. (n = 11)
© Copyright Policy
Related In: Results  -  Collection

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

pone.0129952.g003: Hemodynamic influences on gene expression.Asynchronous hemodynamic conditions significantly increased the expression of the adhesion molecules CDH5 and VCAM-1 (B). Asynchronous hemodynamic conditions significantly increased EPCR and SCD1 mRNA levels (C). Asynchronous hemodynamic conditions significantly increased the mRNA levels of transcription regulators OLR-1, ADFP, and SCARB1 (D) **p < 0.05, * p<0.1 indicate significant differences for SPA 0° with respect to control or SPA -180° with respect to control. An overbar indicates pairwise significant difference between SPA 0° and SPA -180°. (n = 11)
Mentions: We analyzed the regulation of mRNA levels for vasoactive genes endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1) and cyclooxygenase-2 (COX-2). WSS and CS induced 2.3 and 3.3 fold increase in eNOS mRNA levels for SPA = 0° and SPA = -180°, respectively, compared to static control, indicating that BAECs were responsive to WSS and CS (Fig 3A). Asynchronous hemodynamics increased ET-1 mRNA levels ~1.55-fold relative to static controls. Synchronous hemodynamics increased COX-2 mRNA levels ~3.55-fold relative to static control. There were no significant differences between synchronous and asynchronous conditions for any of these genes. WSS and CS showed a significant difference from static controls in ET-1 mRNA levels for SPA = -180° but not SPA = 0°. WSS and CS induced 3.3 and 2.2-fold increases in COX-2 mRNA levels for SPA = 0° and SPA = -180° respectively. Only SPA = 0° induced a significant increase in COX-2 mRNA levels compared with static controls.

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