Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress
Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress
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DOI：
10.1161/circulationaha.105.590018
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发表时间：
2006-06-13
期刊：
影响因子：
37.8
通讯作者：
de Crom, Rini
中科院分区：
文献类型：
--
作者：
Cheng, Caroline;Tempel, Dennie;de Crom, Rini
背景-动脉粥样硬化病变主要发生在弯曲动脉和侧支附近，在这些部位出现低剪切应力或振荡剪切应力模式，提示存在因果关系。然而，剪切应力对斑块脆弱性的影响是未知的，因为缺乏一个适当的体内模型排除因果study.Methods和结果-我们开发了一种血管周围的剪切应力修饰剂，诱导区域降低，增加，降低/振荡（即，与涡流）剪切应力在小鼠颈动脉和研究斑块的形成和组成。动脉粥样硬化病变总是在剪切应力或涡流降低的区域发展，而剪切应力增加的区域受到保护。低切应力损伤更大（内膜/中膜，1.38 +/- 0.68 vs 0.22 +/- 0.04）;平滑肌细胞较少（1.9 +/- 1.6% vs 26.3 +/- 9.7%），胶原蛋白较少（15.3 +/- 1.0% vs 22.2 +/- 1.0%），以及更多脂质（15.8 +/- 0.9%对10.2 +/- 0.5%）;并显示出比振荡剪切应力损伤更多的向外血管重塑（214 +/- 19%对117 +/- 9%）。致动脉粥样硬化炎症介质和基质金属蛋白酶活性的表达在低切应力区域更高。自发性和血管紧张素II诱导的斑块内血栓发生在降低的剪切应力regions.Conclusions -降低的剪切应力和振荡剪切应力都是斑块形成的必要条件。较低的剪切应力诱导更大的病变与易损斑块表型，而振荡剪切应力的涡流诱导稳定的病变。
Background - 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.Methods and Results - 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.Conclusions - 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.