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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3691-3698.
Prepublished online as a Blood First Edition Paper on August 16, 2005; DOI 10.1182/blood-2005-06-2326.
Previous Article | Next Article 
Submitted June 14, 2005
Accepted July 22, 2005
Shear stress affects the intracellular distribution of eNOS: direct demonstration by a novel in vivo technique
Caroline Cheng, Rien van Haperen, Monique de Waard, Luc C van Damme, Denie Tempel, Laurens Hanemaaijer, Gert W van Capellen, Joop Bos, Cornelis J Slager, Dirk J Duncker, Anton F van der Steen, Rini de Crom, and Rob Krams*
Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands
Cell Biology and Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands
Development and Reproduction, Erasmus University Medical Center, Rotterdam, The Netherlands
Experimental Medical Instrumentation, Erasmus University Medical Center, Rotterdam, The Netherlands
Cell Biology and Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands; Vascular Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
* Corresponding author; email: r.rkams{at}erasmusmc.nl.
The focal location of atherosclerosis in the vascular tree is correlated with local variations in shear stress. We developed a method to induce defined variations in shear stress in a straight vessel segment of a mouse. To this end, a cylinder with a tapered lumen is placed around the carotid artery, inducing a high shear stress field. Concomitantly, regions of low shear stress and oscillatory shear stress are created upstream and downstream of the device, respectively. This device was used in mice transgenic for an eNOS-GFP fusion gene. We observed a strong induction of eNOS-GFP mRNA expression in the high shear stress region compared with the other regions (P< 0.05). Quantification of eNOS-GFP fluorescence or of immuno-reactivity to the Golgi complex or to PECAM-1 showed an increase in the high shear stress region (P< 0.05) compared with non-treated carotid arteries. Co-localization of eNOS-GFP with either the Golgi complex or PECAM-1 also responded to alterations of shear stress.
In conclusion, we showed a direct response of mRNA and protein expression in vivo to induced variations of shear stress. This model provides the opportunity to study the relation between shear stress alterations, gene expression and atherosclerosis.

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