Endogenous Renovascular Hypertension Combined With Low Shear Stress Induces Plaque Rupture in Apolipoprotein E-Deficient Mice
Endogenous Renovascular Hypertension Combined With Low Shear Stress Induces Plaque Rupture in Apolipoprotein E-Deficient Mice
复制标题
内源性肾血管性高血压联合低剪切应力诱导载脂蛋白 E 缺陷小鼠斑块破裂
DOI：
10.1161/atvbaha.111.236158
复制
发表时间：
2012-10-01
影响因子：
8.7
通讯作者：
He, Ben
中科院分区：
文献类型：
--
作者：
Jin, Shu-xuan;Shen, Ling-hong;He, Ben
目的：建立自发性动脉粥样硬化斑块破裂伴腔内血栓的小鼠模型。方法与结果：8周龄载脂蛋白e缺陷小鼠左肾动脉和左颈总动脉联合部分结扎可引起内源性肾血管性高血压和左颈总动脉局部低振荡剪应力。8周后，50%（10/20）的小鼠发现新鲜的左侧颈总动脉管腔血栓伴严重斑块负担。组织学分析显示左侧颈总动脉病变均有易损特征，50%（5/10）小鼠斑块破裂伴管腔血栓形成。80%（8/10）小鼠可见斑块内出血，呈多层不连续性。进一步的实验表明，血压升高和血管紧张素- ii都有助于斑块的进展和易感性。减少的内膜胶原蛋白与增加的胶原酶活性和基质金属蛋白酶表达也导致斑块破坏。结论：我们建立了一种具有高腔内血栓发生率的自发性斑块破裂小鼠模型。该模型不仅很好地概括了人类斑块破裂的病理生理过程，而且生成简单、快速、高效。（中华动脉血管杂志，2012;32:2372-2379）
Objective-The development of a murine model of spontaneous atherosclerotic plaque rupture with luminal thrombus.Methods and Results-Combined partial ligation of the left renal artery and left common carotid artery in 8-week-old apolipoprotein E-deficient mice induced endogenous renovascular hypertension and local low oscillatory shear stress in the left common carotid artery. After 8 weeks, a fresh left common carotid artery lumen thrombus associated with severe plaque burden was found in 50% (10/20) of the mice. Histological analyses indicated that all left common carotid artery lesions had vulnerable features, and 50% (5/10) of the mice showed plaque rupture with a lumen thrombus. Multiple layers with layering discontinuity and intraplaque hemorrhages were found in 80% (8/10) of the mice. Further experiments showed that both increased blood pressure, and angiotensin-II contributed to plaque progression and vulnerability. Decreased intimal collagen associated with increased collagenase activity and matrix metalloproteinase expression also resulted in plaque disruption.Conclusion-We demonstrate a murine model of spontaneous plaque rupture with a high incidence of luminal thrombus. The model not only nicely recapitulates the pathophysiological processes of human plaque rupture but it is also simple, fast, and highly efficient to generate. (Arterioscler Thromb Vasc Biol. 2012; 32: 2372-2379.)