Limits...
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

Simultaneous WSS and CS on EC are characterized by the SPA.Blood flow in the axial direction induces wall shear stress (WSS) and the changes in pressure during the cardiac cycle induce circumferential strain and circumferential stress (CS) on the EC lining the wall of the blood vessel. Due to impedance of the distal circulation, local inertial effects associated with flow in larger vessels and arterial geometry, there is a time lag between WSS and CS characterized by the stress phase angle—SPA = φ(CS-WSS)
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4492743&req=5

pone.0129952.g001: Simultaneous WSS and CS on EC are characterized by the SPA.Blood flow in the axial direction induces wall shear stress (WSS) and the changes in pressure during the cardiac cycle induce circumferential strain and circumferential stress (CS) on the EC lining the wall of the blood vessel. Due to impedance of the distal circulation, local inertial effects associated with flow in larger vessels and arterial geometry, there is a time lag between WSS and CS characterized by the stress phase angle—SPA = φ(CS-WSS)

Mentions: The fluid wall shear stress (WSS) driven by pulsatile blood flow and the solid circumferential stress (CS) driven by pulsatile blood pressure and associated strain, act simultaneously on endothelial cells (EC) lining blood vessels modulating their biological activity. Due to distal impedance at a vascular site of interest (global effect) and the inertial effects of blood flow at the site (local effect), a time lag arises between CS and WSS that is referred to as the “Stress phase angle”—SPA [1] (Fig 1). The SPA has been shown to play a role in regulating the release of vasoactive molecules such as nitric oxide (NO), endothelin-1 (ET-1), and prostacyclin (PGI2) in vitro. The production of NO and PGI2 by bovine aortic endothelial cells (BAEC) were suppressed, while the production of the vasoconstrictor ET-1 was increased under highly asynchronous hemodynamic conditions compared with more synchronous hemodynamic conditions [1]. Recent computational and theoretical studies of SPA have been carried out for a coronary artery [2], the carotid bifurcation [3], end-to-end anastomosis [4], and the EC plasma membrane [5], showing that large negative SPA occurs in regions of the circulation where atherosclerosis and intimal hyperplasia are localized. In support of these findings, in vivo studies showed that coronary arteries with highly asynchronous hemodynamics exhibited a pathological gene expression pattern for a limited number of genes [6] and that intimal hyperplasia does not correlate with WSS alone in coronary arteries [7]. Other recent reviews and computational analyses further support the idea that WSS characteristics alone do not completely account for the localization of vascular disease [7–9]. These observations suggest that hemodynamic factors other than WSS may play a critical role in localization and development of atherosclerosis.


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

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

Simultaneous WSS and CS on EC are characterized by the SPA.Blood flow in the axial direction induces wall shear stress (WSS) and the changes in pressure during the cardiac cycle induce circumferential strain and circumferential stress (CS) on the EC lining the wall of the blood vessel. Due to impedance of the distal circulation, local inertial effects associated with flow in larger vessels and arterial geometry, there is a time lag between WSS and CS characterized by the stress phase angle—SPA = φ(CS-WSS)
© Copyright Policy
Related In: Results  -  Collection

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

pone.0129952.g001: Simultaneous WSS and CS on EC are characterized by the SPA.Blood flow in the axial direction induces wall shear stress (WSS) and the changes in pressure during the cardiac cycle induce circumferential strain and circumferential stress (CS) on the EC lining the wall of the blood vessel. Due to impedance of the distal circulation, local inertial effects associated with flow in larger vessels and arterial geometry, there is a time lag between WSS and CS characterized by the stress phase angle—SPA = φ(CS-WSS)
Mentions: The fluid wall shear stress (WSS) driven by pulsatile blood flow and the solid circumferential stress (CS) driven by pulsatile blood pressure and associated strain, act simultaneously on endothelial cells (EC) lining blood vessels modulating their biological activity. Due to distal impedance at a vascular site of interest (global effect) and the inertial effects of blood flow at the site (local effect), a time lag arises between CS and WSS that is referred to as the “Stress phase angle”—SPA [1] (Fig 1). The SPA has been shown to play a role in regulating the release of vasoactive molecules such as nitric oxide (NO), endothelin-1 (ET-1), and prostacyclin (PGI2) in vitro. The production of NO and PGI2 by bovine aortic endothelial cells (BAEC) were suppressed, while the production of the vasoconstrictor ET-1 was increased under highly asynchronous hemodynamic conditions compared with more synchronous hemodynamic conditions [1]. Recent computational and theoretical studies of SPA have been carried out for a coronary artery [2], the carotid bifurcation [3], end-to-end anastomosis [4], and the EC plasma membrane [5], showing that large negative SPA occurs in regions of the circulation where atherosclerosis and intimal hyperplasia are localized. In support of these findings, in vivo studies showed that coronary arteries with highly asynchronous hemodynamics exhibited a pathological gene expression pattern for a limited number of genes [6] and that intimal hyperplasia does not correlate with WSS alone in coronary arteries [7]. Other recent reviews and computational analyses further support the idea that WSS characteristics alone do not completely account for the localization of vascular disease [7–9]. These observations suggest that hemodynamic factors other than WSS may play a critical role in localization and development of atherosclerosis.

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