Response to Letter Regarding Article, “Atherosclerotic Lesion Size and Vulnerability Are Determined by Patterns of Fluid Shear Stress”
We thank Dr Jankowski for his interest in our article.1 The major conclusions from our work are that both reduced and oscillating shear stress are proatherogenic but that they induce different plaque compositions. Reduced shear stress induces vulnerable plaques, and oscillating shear stress induces stable plaques. In addition, we found that high shear stress is atheroprotective. Dr Jankowski challenges our last conclusion, referring to the analogy between the cast model we developed and a previously described wrap model,2 which is atheroprotective because of reduced tensile stress rather than high shear stress.
We believe that it is difficult to directly compare the 2 animal models. Tropea et al2 used rabbits in which hypertension was induced by aortic banding. After only 3 weeks of an atherogenic diet, a cell-rich intimal hyperplasia lesion was formed, which could be prevented by a wrap reducing the wall motion. In the mice we used, advanced atherosclerotic lesions with a necrotic core and characteristics of a vulnerable plaque were formed after 9 weeks of an atherogenic diet. This type of lesion did not develop in the rabbits, and thus potential prevention by the wrap has not been demonstrated.
Dr Jankowski also suggests that the vulnerable plaque phenotype of the lesions proximal to the cast might be related to increased tensile stress. However, blood pressure, diameter, and vessel wall thickness were not affected by cast placement; hence, wall stress remained unchanged during the early phase. During the process of plaque formation, wall thickness increases, thereby reducing wall stress rather than increasing it.
We do agree that the vessel segment within the cast is exposed to both increased shear stress and reduced tensile stress. To study the effects of tensile stress per se, one could implement the nonconstrictive control cast in an atherosclerosis-prone area, such as a low–shear stress area. At present, the potential atheroprotective effect of reduced tensile stress in addition to that of increased shear stress remains to be proven.
Cheng C, Tempel D, van Haperen R, van der Baan A, Grosveld F, Daemen MJ, Krams R, de Crom R. Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation. 2006; 113: 2744–2753.
Tropea BI, Schwarzacher SP, Chang A, Asvar C, Huie P, Sibley RK, Zarins CK. Reduction of aortic wall motion inhibits hypertension-mediated experimental atherosclerosis. Arterioscler Thromb Vasc Biol. 2000; 20: 2127–2133.