Cheng Caroline, Tempel Dennie, van Haperen Rien, van der Baan Arjen, Grosveld Frank, Daemen Mat J A P, Krams Rob, de Crom Rini
Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Circulation. 2006 Jun 13;113(23):2744-53. doi: 10.1161/CIRCULATIONAHA.105.590018. Epub 2006 Jun 5.
Atherosclerotic lesions are predominantly observed in curved arteries and near side branches, where low or oscillatory shear stress patterns occur, suggesting a causal connection. However, the effect of shear stress on plaque vulnerability is unknown because the lack of an appropriate in vivo model precludes cause-effect studies.
We developed a perivascular shear stress modifier that induces regions of lowered, increased, and lowered/oscillatory (ie, with vortices) shear stresses in mouse carotid arteries and studied plaque formation and composition. Atherosclerotic lesions developed invariably in the regions with lowered shear stress or vortices, whereas the regions of increased shear stress were protected. Lowered shear stress lesions were larger (intima/media, 1.38+/-0.68 versus 0.22+/-0.04); contained fewer smooth muscle cells (1.9+/-1.6% versus 26.3+/-9.7%), less collagen (15.3+/-1.0% versus 22.2+/-1.0%), and more lipids (15.8+/-0.9% versus 10.2+/-0.5%); and showed more outward vascular remodeling (214+/-19% versus 117+/-9%) than did oscillatory shear stress lesions. Expression of proatherogenic inflammatory mediators and matrix metalloproteinase activity was higher in the lowered shear stress regions. Spontaneous and angiotensin II-induced intraplaque hemorrhages occurred in the lowered shear stress regions only.
Lowered shear stress and oscillatory shear stress are both essential conditions in plaque formation. Lowered shear stress induces larger lesions with a vulnerable plaque phenotype, whereas vortices with oscillatory shear stress induce stable lesions.
动脉粥样硬化病变主要出现在弯曲动脉和分支附近，这些部位存在低剪切应力或振荡剪切应力模式，提示二者存在因果关系。然而，由于缺乏合适的体内模型，无法进行因果关系研究，因此剪切应力对斑块易损性的影响尚不清楚。
我们研发了一种血管周围剪切应力调节剂，可在小鼠颈动脉中诱导出剪切应力降低、升高以及降低/振荡（即伴有涡流）的区域，并研究斑块的形成和组成。在剪切应力降低或存在涡流的区域总是会形成动脉粥样硬化病变，而剪切应力升高的区域则受到保护。剪切应力降低区域的病变更大（内膜/中膜，1.38±0.68 对 0.22±0.04）；平滑肌细胞较少（1.9±1.6%对 26.3±9.7%），胶原蛋白较少（15.3±1.0%对 22.2±1.0%），脂质较多（15.8±0.9%对 10.2±0.5%）；与振荡剪切应力病变相比，血管向外重塑更明显（214±19%对 117±9%）。促动脉粥样硬化炎症介质的表达和基质金属蛋白酶活性在剪切应力降低区域更高。仅在剪切应力降低区域发生自发性和血管紧张素 II 诱导的斑块内出血。
剪切应力降低和振荡剪切应力都是斑块形成的必要条件。剪切应力降低会诱导形成具有易损斑块表型的更大病变，而伴有振荡剪切应力的涡流会诱导形成稳定病变。
