The effect of physiological cyclic stretch on the cell morphology, cell orientation and protein expression of endothelial cells
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In vivo, endothelial cells are constantly exposed to pulsatile shear and tensile stresses. The main aim of this study was to design and build a physiological simulator, which reproduced homogenous strain profiles of the tensile strain experienced in vivo, and to investigate the effect of this cyclic tensile strain on the cell morphology, cell orientation and protein expression of endothelial cells. The biological response of human umbilical vein endothelial cells to a uniaxial cyclic stretch, in this newly developed simulator, was examined experimentally using immunohistostaining and confocal imaging and it was found that the cells elongated and oriented at 58.9° ± 4.5°. This value was compared to a mathematical model where it was revealed that endothelial cells would orient at an angle of 60°. This model also revealed that endothelial cells have an axial strain threshold value of 1.8% when exposed to a 10% cyclic strain at 1 Hz for 3 h. Cells cultured under conditions of cyclic strain showed increased ICAM-1 immunostaining when compared to static cells whereas, a marked decrease in the levels of VCAM-1 receptor staining was also observed. Haemodynamic stresses can modulate the endothelial cell adhesion response in vivo thus, taken together; this data validates the bioreactor as replicating the physiological environment.
This work was supported by the Programme for Research in Third Level Institutions (PRTLI), administered by the Higher Education Authority (HEA), Science Foundation Ireland and the Embark Initiative, operated by the Irish Research Council for Science, Engineering and Technology (IRCSET). The authors would like to acknowledge the help and support of Dr Bruce P. Murphy, Dr Margaret O’Brien, Dr. Michael Ball, Dr Eadaoin Timmins, Mr William Brennan and Mr. Ken Pascal, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.
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