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| Content Provider | PubMed Central |
|---|---|
| Author | Guillermo, García-cardeña Jason, Comander Anderson, Keith R. Blackman, Brett R. Gimbrone, Michael A. |
| Copyright Year | 2001 |
| Abstract | One of the striking features of vascular endothelium, thesingle-cell-thick lining of the cardiovascular system, is itsphenotypic plasticity. Various pathophysiologic factors, such ascytokines, growth factors, hormones, and metabolic products, canmodulate its functional phenotype in health and disease. In addition tothese humoral stimuli, endothelial cells respond to their biomechanicalenvironment, although the functional implications of this biomechanicalparadigm of activation have not been fully explored. Here we describe ahigh-throughput genomic analysis of modulation of gene expressionobserved in cultured human endothelial cells exposed to two welldefined biomechanical stimuli—a steady laminar shear stress and aturbulent shear stress of equivalent spatial and temporal averageintensity. Comparison of the transcriptional activity of 11,397 uniquegenes revealed distinctive patterns of up- and down-regulationassociated with each type of stimulus. Cluster analyses oftranscriptional profiling data were coupled with other molecular andcell biological techniques to examine whether these global patterns ofbiomechanical activation are translated into distinct functionalphenotypes. Confocal immunofluorescence microscopy of structural andcontractile proteins revealed the formation of a complex apicalcytoskeleton in response to laminar shear stress. Cell cycle analysisdocumented different effects of laminar and turbulent shear stresses oncell proliferation. Thus, endothelial cells have the capacity todiscriminate among specific biomechanical forces and to translate theseinput stimuli into distinctive phenotypes. The demonstration thathemodynamically derived stimuli can be strong modulators ofendothelial gene expression has important implications for ourunderstanding of the mechanisms of vascular homeostasis andatherogenesis. |
| Related Links | http://dx.doi.org/10.1073/pnas.071052598 |
| Ending Page | 4485 |
| Page Count | 8 |
| Starting Page | 4478 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 98 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2001-04-10 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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