Endothelial cell response to biomechanical forces under simulated vascular loading conditions

Punchard, Marie Anne; Stenson-Cox, C.; O’Cearbhaill, Eoin D.; Lyons, E. T.; Gundy, Sarah L.; Murphy, Lisa; Pandit, Abhay; McHugh, Peter E.; Barron, Valerie

doi:10.1016/j.jbiomech.2007.03.029

Cited by 39 publications

(28 citation statements)

References 22 publications

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“…Nonetheless, a number of systems have been developed to examine the effects of either shear stress or cyclic stretch on the gene expression of endothelial cells. 3,11,35,39,42,47,54 Moreover, as altered gene expression has been seen to occur post stent deployment, the development of a coronary artery simulator that could replicate the biomechanical forces observed in vivo would provide an alternative approach to the shortcomings described by Edelman et al 14 of studying clinical end points alone.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Human Endothelial Cells Post Stent Deployment in a Cardiovascular Simulator In Vitro

et al. 2009

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Percutaneous stent implantation has revolutionized the clinical treatment of occluded arteries. Nevertheless, there is still a large unmet need to prevent re-occlusion after implantation. Consequently, a niche exists for a cost-effective pre-clinical method of evaluating novel interventional devices in human models. Therefore, the development of a coronary model artery offers tremendous potential for the treatment of endothelial cell dysfunction and restenosis. As a first step, we employ tissue-engineering principles to examine the effect of stent deployment upon endothelial cells in a tubular in vitro system capable of replicating the coronary artery biomechanical environment. In particular, the cellular and molecular changes pertaining to inflammation, proliferation, and death were assessed after stent deployment. Real-time quantitative PCR demonstrated increased expression of genes encoding for E-Selectin, ICAM-1, and VCAM-1; markers associated with an inflammatory response in vivo. Further, an increase in the pro-apoptotic protein Bax was paralleled with a decrease in the anti-apoptotic protein Bcl-2; however, apoptotic morphology was not observed. Interestingly, transcription of c-fos increased, whereas Ki67 levels fell over the same period. One hypothesis is that these results are in response to the altered local hemodynamic environment induced by stent deployment. Most significantly, this study highlights the potential of a biomimetic hemodynamic bioreactor combined with a gene expression analysis to evaluate, with greater specificity, the performance and interaction of stents with the endothelial layer in a controlled environment.

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Section: Introductionmentioning

confidence: 99%

Evaluation of Human Endothelial Cells Post Stent Deployment in a Cardiovascular Simulator In Vitro

et al. 2009

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“…This difference is likely due to exposure to hydrostatic pressure, given that other experiments have demonstrated that mRNA expression of E-selectin is upregulated in non-stimulated ECs exposed to a hydrostatic pressure of 100 mmHg, while mRNA expression of VCAM-1 was downregulated (22) . In addition, previous literature reports that there are no changes in the protein expression of E-selectin in ECs exposed to 4 cmH 2 O (= 3.0 mmHg) for 24 hours (23) ，but that expression of E-selectin increased in ECs exposed to a pulsatile flow with a pressure of 90 ± 30 mmHg and a shear stress of 0.5 Pa for 24 hours (24) ．These results suggest that physiological hydrostatic pressure may upregulate E-selectin expression. Similarly, physiological shear stress upregulates ICAM-1 expression (9) (10) , and also increases ICAM-1 expression induced by TNF-α (5)(14) (15) although it decreases VCAM-1 and E-selectin expression induced by TNF-α (5)(13)~ (16) .…”

Section: Discussionmentioning

confidence: 94%

Combinations of Hydrostatic Pressure and Shear Stress Time-dependently Decrease E-selectin, VCAM-1 and ICAM-1 Expression Induced by Tumor Necrosis Factor-Alpha in Cultured Endothelial Cells

Nakadate

Sekizuka

Aomura

et al. 2012

JBSE

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Endothelial cells (ECs) are constantly subjected to shear stress, a tangential stress generated by blood flow, and hydrostatic pressure, a normal stress generated by blood pressure. Using a perfusion system that enables the independent control of flow volume and pressure, we investigated the effect of this combined stress on adhesion molecule expression in cytokine-stimulated cultured ECs. Human umbilical vein endothelial cells were incubated with 25 ng/ml tumor necrosis factor-alpha (TNF-α) for 6 hours. Activated ECs were then exposed to pulsatile flow (a shear stress of 1.5 ± 0.3 Pa, and a hydrostatic pressure of 100 ± 20 mmHg) for 1-24 hours. After exposure to pulsatile flow, endothelial selectin (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were stained and observed using fluorescence microscopy. Results showed that E-selectin was expressed in approximately 30% of the total ECs after incubation with TNF-α, however, TNF-α-induced E-selectin expression was decreased after 1 hour of exposure to pulsatile flow resulting in E-selectin expression in under 10% of total ECs at 24 hours. VCAM-1 was expressed in approximately 75% of the total ECs after incubation with TNF-α, however, TNF-α-induced VCAM-1 expression was decreased after 6 hours of exposure to pulsatile flow resulting in VCAM-1 expression in approximately 40% of the total ECs at 24 hours. ICAM-1 was expressed in all ECs after incubation with TNF-α, however, TNF-α-induced ICAM-1 expression was decreased after 12 hours of exposure to pulsatile flow resulting in ICAM-1 expression in approximately 40% of the total ECs at 24 hours. These results suggest that combined stress time-dependently suppresses overexpression of cytokine-induced adhesion molecules in ECs.

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“…[10,12] hMSC Metabolism is Unaffected by the Presence of the Scaffold Cytotoxicity test methods were employed to examine the cell response in the presence of the CNT/PLA scaffolds as described previously. [13] The hMSC were seeded at a density of 20 000 cells Á cm À2 and maintained for 24 h at 37 8C in a humidified atmosphere of 5% CO 2 at 37 8C. Thereafter, scaffold strips, 1/10 of the total area of the well were placed directly on the cells and incubated for an additional 24 h. An AlamarBlue (AB) assay (Molecular Probes) was then employed to examine the metabolic activity of the cells by measuring the fluorescence intensity (530 nm excitation/590 nm emission) on a microplate fluorescence reader (FLX800, Biotek Instruments Inc.).…”

Section: Scanning Electron Microscopy (Sem)mentioning

confidence: 99%

In vitro Characterization of an Electroactive Carbon‐Nanotube‐Based Nanofiber Scaffold for Tissue Engineering

Mackle¹,

Blond²,

Mooney³

et al. 2011

Macromolecular Bioscience

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In an effort to reduce organ replacement and enhance tissue repair, there has been a tremendous effort to create biomechanically optimized scaffolds for tissue engineering applications. In contrast, the development and characterization of electroactive scaffolds has attracted little attention. Consequently, the creation and characterization of a carbon nanotube based poly(lactic acid) nanofiber scaffold is described herein. After 28 d in physiological solution at 37 °C, a change in the mass, chemical properties and polymer morphology is seen, while the mechanical properties and physical integrity are unaltered. No adverse cytotoxic affects are seen when mesenchymal stem cells are cultured in the presence of the scaffold. Taken together, these data auger well for electroactive tissue engineering.

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Endothelial cell response to biomechanical forces under simulated vascular loading conditions

Cited by 39 publications

References 22 publications

Evaluation of Human Endothelial Cells Post Stent Deployment in a Cardiovascular Simulator In Vitro

Evaluation of Human Endothelial Cells Post Stent Deployment in a Cardiovascular Simulator In Vitro

Combinations of Hydrostatic Pressure and Shear Stress Time-dependently Decrease E-selectin, VCAM-1 and ICAM-1 Expression Induced by Tumor Necrosis Factor-Alpha in Cultured Endothelial Cells

In vitro Characterization of an Electroactive Carbon‐Nanotube‐Based Nanofiber Scaffold for Tissue Engineering

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