| 1. |
- Andersson, Maria, 1975, et al.
(författare)
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Differential global gene expression response patterns of human endothelium exposed to shear stress and intraluminal pressure
- 2005
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Ingår i: J Vasc Res. - : S. Karger AG. - 1018-1172. ; 42:5, s. 441-52
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the global gene expression response of endothelium exposed to shear stress and intraluminal pressure and tested the hypothesis that the two biomechanical forces induce a differential gene expression response pattern. Intact living human conduit vessels (umbilical veins) were exposed to normal or high intraluminal pressure, or to low or high shear stress in combination with a physiological level of the other force in a unique vascular ex vivo perfusion system. Gene expression profiling was performed by the Affymetrix microarray technology on endothelial cells isolated from stimulated vessels. Biomechanical forces were found to regulate a very large number of genes in the vascular endothelium. In this study, 1,825 genes were responsive to mechanical forces, which corresponds to 17% of the expressed genes. Among pressure-responsive genes, 647 genes were upregulated and 519 genes were down regulated, and of shear stress-responsive genes, 133 genes were upregulated and 771 down regulated. The fraction of genes that responded to both pressure and shear stimulation was surprisingly low, only 13% of the regulated genes. Our results indicate that the two different stimuli induce distinct gene expression response patterns, which can also be observed when studying functional groups. Considering the low number of overlapping genes, we suggest that the endothelial cells can distinguish between shear stress and pressure stimulation.
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| 2. |
- Bergh, Niklas, 1979, et al.
(författare)
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A new biomechanical perfusion system for ex vivo study of small biological intact vessels
- 2005
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Ingår i: Ann Biomed Eng. - : Springer Science and Business Media LLC. - 0090-6964. ; 33:12, s. 1808-18
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Tidskriftsartikel (refereegranskat)abstract
- The vascular endothelium transduces physical stimuli within the circulation into physiological responses, which influence vascular remodelling and tissue homeostasis. Therefore, a new computerized biomechanical ex vivo perfusion system was developed, in which small intact vessels can be perfused under well-defined biomechanical forces. The system enables monitoring and regulation of vessel lumen diameter, shear stress, mean pressure, variable pulsatile pressure and flow profile, and diastolic reversal flow. Vessel lumen measuring technique is based on detection of the amount of flourescein over a vessel segment. A combination of flow resistances, on/off switches, and capacitances creates a wide range of pulsatile pressures and flow profiles. Accuracy of the diameter measurement was evaluated. The diameters of umbilical arteries were measured and compared with direct ultrasonographic measurement of the vessel diameter. As part of the validation the pulsatile pressure waveform was altered, e.g., in terms of pulse pressure, frequency, diastolic shape, and diastolic reversal flow. In a series of simulation experiments, the hemodynamic homeostasis functions of the system were successfully challenged by generating a wide range of vascular diameters in artificial and intact human vessels. We conclude that the system presented may serve as a methodological and technical platform when performing advanced hemodynamic stimulation protocols.
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| 3. |
- Doroudi, Roya, 1967, et al.
(författare)
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Methodological studies of multiple reference genes as endogenous controls in vascular gene expression studies
- 2005
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Ingår i: Endothelium. - : Informa UK Limited. - 1062-3329 .- 1029-2373. ; 12:5-6, s. 215-23
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Tidskriftsartikel (refereegranskat)abstract
- Detection and quantification of differentially expressed genes requires valid and reliable references to control for error variability introduced by preparatory procedures or efficiency of reverse transcription and polymerase chain reaction (PCR) amplification conditions. So-called housekeeping genes are frequently used as endogenous standards, based on the assumption that they are constitutively expressed and independent of experimental conditions. However, if the influence of experimental stimuli is to be analyzed, it cannot a priori be assumed that their expression is unaffected by stimulation. In the present study, the authors studied the expression of different housekeeping genes in the vascular endothelium of intact conduit vessels perfused in a unique biomechanical perfusion model. Ten control gene candidates were investigated by microarray expression analysis. Further, five of these genes were systematically analyzed by real-time reverse transcriptase (RT)-PCR gene quantification and their suitability as reference genes were evaluated. On the basis of these findings, the authors suggest criteria for evaluation of endogenous control genes in vascular perfusion studies.
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