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An in vivo murine model of low-magnitude oscillatory wall shear stress to address the molecular mechanisms of mechanotransduction--brief report.

ABSTRACT: Current understanding of shear-sensitive signaling pathways has primarily been studied in vitro largely because of a lack of adequate in vivo models. Our objective was to develop a simple and well-characterized murine aortic coarctation model to acutely alter the hemodynamic environment in vivo and test the hypothesis that endothelial inflammatory protein expression is acutely upregulated in vivo by low-magnitude oscillatory wall shear stress (WSS).Our model uses the shape memory response of nitinol clips to reproducibly induce an aortic coarctation and allow subsequent focal control over WSS in the aorta. We modeled the corresponding hemodynamic environment using computational fluid dynamics and showed that the coarctation produces low-magnitude oscillatory WSS distal to the clip. To assess the biological significance of this model, we correlated WSS to inflammatory protein expression and fatty streak formation. Vascular cell adhesion molecule-1 expression and fatty streak formation were both found to increase significantly in regions corresponding to acutely induced low-magnitude oscillatory WSS.We have developed a novel aortic coarctation model that will be a useful tool for analyzing the in vivo molecular mechanisms of mechanotransduction in various murine models.

SUBMITTER: Willett NJ

PROVIDER: S-EPMC3148257 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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An in vivo murine model of low-magnitude oscillatory wall shear stress to address the molecular mechanisms of mechanotransduction--brief report.

Willett Nick J NJ Long Robert C RC Maiellaro-Rafferty Kathryn K Sutliff Roy L RL Shafer Richard R Oshinski John N JN Giddens Don P DP Guldberg Robert E RE Taylor W Robert WR

Arteriosclerosis, thrombosis, and vascular biology 20100812 11

<h4>Objective</h4>Current understanding of shear-sensitive signaling pathways has primarily been studied in vitro largely because of a lack of adequate in vivo models. Our objective was to develop a simple and well-characterized murine aortic coarctation model to acutely alter the hemodynamic environment in vivo and test the hypothesis that endothelial inflammatory protein expression is acutely upregulated in vivo by low-magnitude oscillatory wall shear stress (WSS).<h4>Methods and results</h4>O ...[more]

PMID: 20705917

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Project description:IntroductionWall shear stress (WSS) and oscillatory shear index (OSI) are associated with atherosclerotic disease. Both parameters are derived from blood velocities, which can be measured with phase-contrast MRI (PC-MRI). Limitations in spatiotemporal resolution of PC-MRI are known to affect these measurements. Our aim was to investigate the effect of spatiotemporal resolution using a carotid artery phantom.MethodsA carotid artery phantom was connected to a flow set-up supplying pulsatile flow. MRI measurement planes were placed at the common carotid artery (CCA) and internal carotid artery (ICA). Two-dimensional PC-MRI measurements were performed with thirty different spatiotemporal resolution settings. The MRI flow measurement was validated with ultrasound probe measurements. Mean flow, peak flow, flow waveform, WSS and OSI were compared for these spatiotemporal resolutions using regression analysis. The slopes of the regression lines were reported in %/mm and %/100ms. The distribution of low and high WSS and OSI was compared between different spatiotemporal resolutions.ResultsThe mean PC-MRI CCA flow (2.5±0.2mL/s) agreed with the ultrasound probe measurements (2.7±0.02mL/s). Mean flow (mL/s) depended only on spatial resolution (CCA:-13%/mm, ICA:-49%/mm). Peak flow (mL/s) depended on both spatial (CCA:-13%/mm, ICA:-17%/mm) and temporal resolution (CCA:-19%/100ms, ICA:-24%/100ms). Mean WSS (Pa) was in inverse relationship only with spatial resolution (CCA:-19%/mm, ICA:-33%/mm). OSI was dependent on spatial resolution for CCA (-26%/mm) and temporal resolution for ICA (-16%/100ms). The regions of low and high WSS and OSI matched for most of the spatiotemporal resolutions (CCA:30/30, ICA:28/30 cases for WSS; CCA:23/30, ICA:29/30 cases for OSI).ConclusionWe show that both mean flow and mean WSS are independent of temporal resolution. Peak flow and OSI are dependent on both spatial and temporal resolution. However, the magnitude of mean and peak flow, WSS and OSI, and the spatial distribution of OSI and WSS did not exhibit a strong dependency on spatiotemporal resolution.

Dataset Information

An in vivo murine model of low-magnitude oscillatory wall shear stress to address the molecular mechanisms of mechanotransduction--brief report.

Publications

An in vivo murine model of low-magnitude oscillatory wall shear stress to address the molecular mechanisms of mechanotransduction--brief report.

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