Spontaneous plaque rupture and secondary thrombosis in apolipoprotein E-deficient and LDL receptor-deficient mice
Spontaneous plaque rupture and secondary thrombosis in apolipoprotein E-deficient and LDL receptor-deficient mice
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DOI：
10.1002/path.915
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发表时间：
2001-09-01
影响因子：
7.3
通讯作者：
Palinski, W
中科院分区：
文献类型：
--
作者：
Calara, F;Silvestre, M;Palinski, W
载脂蛋白E缺陷（apoE（-/-））和LDL受体缺陷（LDLR-/-）小鼠会出现广泛的动脉粥样硬化，但这些模型中自发斑块破裂和继发性血栓形成的发生尚未确定。本研究的目的是提供这些小鼠动脉粥样硬化病变急性并发症的组织学证据并评估其患病率。动脉粥样硬化的并发症最初是在先前干预研究中死亡的对照小鼠的主动脉中进行的。然后通过 apoE(-/-) 和 LDLR-/- 小鼠心脏的连续切片对冠状动脉和主动脉起源进行系统评估。在过去的干预研究中，82 只未经治疗的小鼠中有 3 只发现主动脉斑块破裂和/或血栓。对 33 只老年 apoE(-/-) 小鼠（9-20 个月）心脏切片的筛查显示，18 只动物的一根或多根冠状动脉存在广泛的动脉粥样硬化。在三根冠状动脉中，晚期动脉粥样硬化病变内存在充满血液的通道，表明先前存在斑块破裂/血栓事件，随后发生再通。在同一小鼠的主动脉起源中，观察到四个深斑块破裂（或到达坏死核心区域的侵蚀）和源自破裂的动脉粥样硬化病变核心的大血栓。尽管斑块破裂/深度糜烂的发生率远低于人类，但这些观察结果表明，apoE(-/-) 和 LDLR-/- 小鼠中确实发生自发斑块破裂和继发性血栓形成。因此，这些小鼠可能适合研究导致动脉粥样硬化血栓形成并发症的因素。然而，小鼠冠状动脉病变中经常缺乏明确定义的单个纤维帽，限制了它们作为纤维帽破裂模型的有用性。版权所有 (C) 2001 John Wiley & Sons, Ltd.
Apolipoprotein E-deficient (apoE(-/-)) and LDL receptor-deficient (LDLR-/-) mice develop extensive atherosclerosis, but the occurrence of spontaneous plaque rupture and secondary thrombosis in these models has not been established. The goal of this study was to provide histological evidence of acute complications of atherosclerotic lesions in these mice and to assess their prevalence. Complications of atherosclerosis were initially studied in aortas of control mice which died during previous intervention studies. Coronary arteries and the aortic origin were then systematically assessed in serial sections through the heart of apoE(-/-) and LDLR-/- mice. Aortic plaque rupture and/or thrombi were seen in 3 of 82 untreated mice from past intervention studies. Screening of heart sections of 33 older apoE(-/-) mice (age 9-20 months) showed extensive atherosclerosis in one or more coronary arteries of 18 animals. In three coronary arteries, the presence of blood-filled channels within advanced atherosclerotic lesions suggested previous plaque disruption/thrombotic events followed by recanalization. In the aortic origin of the same mice, four deep plaque ruptures (or erosions reaching necrotic core areas) and a large thrombus originating from the core of a disrupted atherosclerotic lesion were observed. Although plaque ruptures/deep erosions were far less frequent than in human populations, these observations demonstrate that spontaneous plaque rupture and secondary thrombosis do occur in apoE(-/-) and LDLR-/- mice. These mice may therefore be suitable for studying factors contributing to thrombotic complications of atherosclerosis. However, the frequent absence of a clearly defined single fibrous cap in murine coronary lesions limits their usefulness as a model of fibrous cap rupture. Copyright (C) 2001 John Wiley & Sons, Ltd.