Search

Atherosclerotic lesions preferentially localize near side branches or curved vessels. During the last few decades, research has been shown that low or low and oscillating shear stress is associated with plaque location. Despite ample evidence, the precise mechanism is unknown. This is mainly because of a lack of appropriate animal models. We describe two novel methods to study the hypothesis that shear stress acts through endothelial gene expression or shear stress acts through localizing of inflammation. Both literature evidence and own findings support a role for both mechanisms in atherosclerosis.

Background: Low wall shear stress (WSS) increases neointimal hyperplasia (NH) in vein grafts and stents. We studied the causal relationship between WSS and NH formation in stents by locally increasing WSS with a flow divider (Anti-Restenotic Diffuser, Endoart SA) placed in the center of the stent., Methods and Results: In 9 rabbits fed a high-cholesterol diet for 2 months to induce endothelial dysfunction, 18 stents were implanted in the right and left external iliac arteries (1 stent per vessel). Lumen diameters were measured by quantitative angiography before and after implantation and at 4-week follow-up, at which time, macrophage accumulation and interruption of the internal elastic lamina was determined. Cross sections of stent segments within the ARED (S+ARED), outside the ARED (S[minus]ARED), and in corresponding segments of the contralateral control stent (SCTRL) were analyzed. Changes in WSS induced by the ARED placement were derived by computational fluid dynamics. Computational fluid dynamics analysis demonstrated that WSS increased from 0.38 to 0.82 N/m2 in the S+ARED immediately after ARED placement. This augmentation of shear stress was accompanied by (1) lower mean late luminal loss by quantitative angiography ([minus]0.23+/-0.22 versus [minus]0.58+/-0.30 mm, P=0.02), (2) reduction in NH (1.48+/-0.58, 2.46+/-1.25, and 2.36+/-1.13 mm2, P<0.01, respectively, for S+ARED, S[minus]ARED, and SCTRL), and (3) a reduced inflammation score and a reduced injury score. Increments in shear stress did not change the relationship between injury score and NH or between inflammation score and NH., Conclusions: The newly developed ARED flow divider significantly increases WSS, and this local increment in WSS is accompanied by a local reduction in NH and a local reduction in inflammation and injury. The present study is therefore the first to provide direct evidence for an important modulating role of shear stress in in-stent neointimal hyperplasia.

Aims Plaque rupture has been associated with a high matrix metalloproteinase (MMP) activity. Recently, regional temperature variations have been observed in atherosclerotic plaques in vivo and ascribed to the presence of macrophages. As macrophages are a major source of MMPs, we examined whether regional temperature changes are related to local MMP activity and macrophage accumulation. [ABSTRACT FROM PUBLISHER]

Aims The purpose of this study was to investigate the relation between acute coronary flow reduction and arterial wall temperature.Methods and results Five pigs with normal coronary arteries were catheterized. Arterial wall temperature was studied with a thermographic system that uses a 4-thermistor sensor tip. Flow velocity was studied at the same time and place with the temperature measurements, using a Doppler wire. In order to modify the coronary flow, a balloon was gradually inflated proximally to the thermographic sensors. Temperature differences and flow velocities were simultaneously recorded.Flow velocities above an average peak velocity (APV) of 9cm/s were associated with unaffected temperature measurements. At flow velocities around 4cm/s, the wall temperature was increased (ΔT=0.015±0.005oC, P∼0.05), following the heart-rate. When flow velocity dropped further below this value, the local wall temperature was logarithmically increased to a maximum value observed at total vessel occlusion (ΔT=0.188±0.023oC, P<0.001).Conclusion The reduction of coronary flow has an effect on the arterial wall temperature. This effect however, appears only below a critical threshold of APV and in a logarithmic fashion. Above this threshold, temperature measurements should be unaffected from flow reductions and related to the regional temperature heterogeneity. [ABSTRACT FROM PUBLISHER]