Hydrostatic pressure and shear stress affect endothelin‐1 and nitric oxide release by endothelial cells in bioreactors

Abstract

Abundant experimental evidence demonstrates that endothelial cells are sensitive to flow; however, the effect of fluid pressure or pressure gradients that are used to drive viscous flow is not well understood. There are two principal physical forces exerted on the blood vessel wall by the passage of intra-luminal blood: pressure and shear. To analyze the effects of pressure and shear independently, these two stresses were applied to cultured cells in two different types of bioreactors: a pressure-controlled bioreactor and a laminar flow bioreactor, in which controlled levels of pressure or shear stress, respectively, can be generated. Using these bioreactor systems, endothelin-1 (ET-1) and nitric oxide (NO) release from human umbilical vein endothelial cells were measured under various shear stress and pressure conditions. Compared to the controls, a decrease of ET-1 production by the cells cultured in both bioreactors was observed, whereas NO synthesis was up-regulated in cells under shear stress, but was not modulated by hydrostatic pressure. These results show that the two hemodynamic forces acting on blood vessels affect endothelial cell function in different ways, and that both should be considered when planning in vitro experiments in the presence of flow. Understanding the individual and synergic effects of the two forces could provide important insights into physiological and pathological processes involved in vascular remodeling and adaptation.

Environmental Control in Flow Bioreactors

“…Table 2 shows that vWF is significantly (p < 0.05) upregulated in all the dynamic conditions with respect to the static control, confirming the role of fluid-induced forces in activating vWF expression [25]. Moreover, vWF fluorescence increases with increasing hydrostatic pressure.…”

“…These results were confirmed by a morphological analysis of the images which indicated an increase of cell size with higher pressures, and signs of cell damage starting from 30 mmHg. Table 2 shows that vWF is significantly (p < 0.05) upregulated in all the dynamic conditions with respect to the static control, confirming the role of fluid-induced forces in activating vWF expression [25]. Moreover, vWF fluorescence increases with increasing hydrostatic pressure.…”

“…For evaluating HUVEC responses, 4 h long experiments were performed, as these cells respond very quickly to physical stimuli, like shear stress or pressure [25,26]. On the other hand, for evaluating the chronic effect of hyperpressure on hepatocytes, we conducted 24 h long experiments.…”

A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

“…Shear stress induces rapid and significant downregulation of ET-1 mRNA expression and peptide release with respect to static conditions in bovine aortic endothelial cells and human umbilical vein endothelial cells. 24,25 ET-1 plays an important role in hypertension. Besides its blood pressure raising effect in human beings, ET-1 induces vascular and myocardial hypertrophies, which are independent risk factors for cardiovascular morbidity and mortality.…”

Possibilities of Enhanced External Counterpulsation Using in Clinical Practice

“…Повышенное напряжение сдвига является главным сти-мулом для выделения эндотелием NO и для расширения сосудов [7,8]. Длительное воздействие низкого напря-жения сдвига стимулирует образование эндотелина, а длительное воздействие повышенного напряжения сдвига уменьшает его уровень [9].…”