Shear stress affects the intracellular distribution of eNOS: direct demonstration by a novel in vivo technique

Abstract

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 was placed around the carotid artery, inducing a high shear stress field. Concomitantly, regions of low shear stress and oscillatory shear stress were created upstream and downstream of the device, respectively. This device was used in mice transgenic for an

Atherosclerotic Lesion Size and Vulnerability Are Determined by Patterns of Fluid Shear Stress

“…Based on measurements in rabbits, 8 it is presumed that also in mice there are spatiotemporal oscillations in shear stress downstream from the cast. We cannot measure this directly in mice, however, because of limitations in resolution.…”

“…Still, we believe that flow reversal does occur downstream from the cast in the mouse model, because in that area, we observed changes in cell shapes in mice transgenic for endothelial nitric oxide synthase (eNOS) fused to green fluorescent protein. 8 To obtain additional evidence for the occurrence of vortices, we performed a detailed analysis using computational fluid dynamics. We reasoned that to document the occurrence of vortices, we needed to focus on changes in direction of the velocity vectors and not on changes in amplitude.…”

“…8 No atherosclerotic lesions were present in the increased shear stress regions 6 weeks after cast placement. These findings are in agreement with the generally accepted notion that plaques do not develop under relatively high shear stress conditions.…”

“…The shear stress values have been derived from measurements of vessel diameter and the velocity of blood flow (Doppler measurements). 8 The authors had full access to the data and take full responsibility for its integrity. All authors have read and agree to the manuscript as written.…”

“…8 The cast imposes a fixed geometry on the vessel wall and thereby causes a gradual stenosis, resulting in increased shear stress in the vessel segment inside the cast, a decrease in blood flow and consequently a lowered shear stress region upstream from the cast, and a vortex downstream from the cast (oscillatory blood flow). The upstream reduction in blood flow is caused by a device-induced, flow-limiting stenosis of Ϸ70%.…”