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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

SPA modulates localization of NFKB p105/p50, NFKB p65 and CDH5.BAEC were exposed to asynchronous or synchornous condition for 7h. Stainings for NFKB p105/p50 (B) and p65 (D) were localized in the citoplasm and the nucleos for EC exposed to SPA = -180. NFKB localization where entirely citoplasmatic for EC exposed to SPA = 0 (A, C). The distribution for CDH5 were continous around the entire periphery of the cells after 7 when cells where exposed to SPA = 0 (E). Exposure of EC to SPA = -180 for 7 hours resulted in an intermitted pattern of CDH5 (F). images showed here are representative resutl from 3 individual experiments.
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pone.0129952.g005: SPA modulates localization of NFKB p105/p50, NFKB p65 and CDH5.BAEC were exposed to asynchronous or synchornous condition for 7h. Stainings for NFKB p105/p50 (B) and p65 (D) were localized in the citoplasm and the nucleos for EC exposed to SPA = -180. NFKB localization where entirely citoplasmatic for EC exposed to SPA = 0 (A, C). The distribution for CDH5 were continous around the entire periphery of the cells after 7 when cells where exposed to SPA = 0 (E). Exposure of EC to SPA = -180 for 7 hours resulted in an intermitted pattern of CDH5 (F). images showed here are representative resutl from 3 individual experiments.

Mentions: NFκB gene expression was significantly up-regulated by SPA = −180° compared to SPA = 0° (Fig 4B). To assess the effects of SPA on the protein expression and localization of NFκB p105/p50 and NFKB p65 we compared the immunostaining of NFκB (p105/p50 and p65) on BAECs exposed to asynchronous or synchronous hemodynamics for 7h. Our results indicate that asynchronous hemodynamics induce the translocation of NFΚB p105/p50 and p65 to the nucleus as shown in the Fig 5b and 5e. The localization of NFκB is entirely cytoplasmic for synchronous hemodynamics (Fig 5a and 5d).


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

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

SPA modulates localization of NFKB p105/p50, NFKB p65 and CDH5.BAEC were exposed to asynchronous or synchornous condition for 7h. Stainings for NFKB p105/p50 (B) and p65 (D) were localized in the citoplasm and the nucleos for EC exposed to SPA = -180. NFKB localization where entirely citoplasmatic for EC exposed to SPA = 0 (A, C). The distribution for CDH5 were continous around the entire periphery of the cells after 7 when cells where exposed to SPA = 0 (E). Exposure of EC to SPA = -180 for 7 hours resulted in an intermitted pattern of CDH5 (F). images showed here are representative resutl from 3 individual experiments.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0129952.g005: SPA modulates localization of NFKB p105/p50, NFKB p65 and CDH5.BAEC were exposed to asynchronous or synchornous condition for 7h. Stainings for NFKB p105/p50 (B) and p65 (D) were localized in the citoplasm and the nucleos for EC exposed to SPA = -180. NFKB localization where entirely citoplasmatic for EC exposed to SPA = 0 (A, C). The distribution for CDH5 were continous around the entire periphery of the cells after 7 when cells where exposed to SPA = 0 (E). Exposure of EC to SPA = -180 for 7 hours resulted in an intermitted pattern of CDH5 (F). images showed here are representative resutl from 3 individual experiments.
Mentions: NFκB gene expression was significantly up-regulated by SPA = −180° compared to SPA = 0° (Fig 4B). To assess the effects of SPA on the protein expression and localization of NFκB p105/p50 and NFKB p65 we compared the immunostaining of NFκB (p105/p50 and p65) on BAECs exposed to asynchronous or synchronous hemodynamics for 7h. Our results indicate that asynchronous hemodynamics induce the translocation of NFΚB p105/p50 and p65 to the nucleus as shown in the Fig 5b and 5e. The localization of NFκB is entirely cytoplasmic for synchronous hemodynamics (Fig 5a and 5d).

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