Mechanisms of Plaque Formation and Rupture
Mechanisms of Plaque Formation and Rupture
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DOI：
10.1161/circresaha.114.302721
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发表时间：
2014-06-06
影响因子：
20.1
通讯作者：
Falk, Erling
中科院分区：
文献类型：
--
作者：
Bentzon, Jacob Fog;Otsuka, Fumiyuki;Falk, Erling
动脉粥样硬化通过管腔狭窄或通过沉淀血栓而导致临床疾病，血栓阻塞血液流向心脏（冠心病）、大脑（缺血性中风）或下肢（外周血管疾病）。这些表现中最常见的是冠心病，包括稳定型心绞痛和急性冠状动脉综合征。动脉粥样硬化是一种脂蛋白驱动的疾病，通过内膜炎症、坏死、纤维化和钙化导致动脉树特定部位的斑块形成。经过几十年的缓慢进展，这些斑块可能突然引起危及生命的冠状动脉血栓形成，表现为急性冠状动脉综合征。大多数情况下，罪魁祸首形态是斑块破裂，暴露出高度血栓形成的、富含红细胞的坏死核心物质。允许发生这种情况的结构要求是极薄的纤维帽，因此，破裂主要发生在定义为薄帽纤维动脉粥样硬化的病变中。在没有破裂的病变（斑块糜烂）上形成血栓也很常见，最常见于病理性内膜增厚或纤维粥样硬化。然而，尽管怀疑冠状动脉痉挛，但斑块侵蚀的机制仍不清楚。钙化结节被认为是老年人高度钙化和迂曲动脉中冠状动脉血栓形成的罕见原因。为了表征斑块的严重性和预后，使用了几个术语。斑块负荷表示疾病的程度，而斑块活性是一个模糊的术语，它可能是指表征进展的几个过程之一。斑块脆弱性描述了短期内有症状血栓形成的风险。在这篇综述中，我们讨论了动脉粥样硬化斑块发生和发展的机制;斑块如何突然沉淀危及生命的血栓;以及斑块负荷、活性和易损性的概念。
Atherosclerosis causes clinical disease through luminal narrowing or by precipitating thrombi that obstruct blood flow to the heart (coronary heart disease), brain (ischemic stroke), or lower extremities (peripheral vascular disease). The most common of these manifestations is coronary heart disease, including stable angina pectoris and the acute coronary syndromes. Atherosclerosis is a lipoprotein-driven disease that leads to plaque formation at specific sites of the arterial tree through intimal inflammation, necrosis, fibrosis, and calcification. After decades of indolent progression, such plaques may suddenly cause life-threatening coronary thrombosis presenting as an acute coronary syndrome. Most often, the culprit morphology is plaque rupture with exposure of highly thrombogenic, red cell-rich necrotic core material. The permissive structural requirement for this to occur is an extremely thin fibrous cap, and thus, ruptures occur mainly among lesions defined as thin-cap fibroatheromas. Also common are thrombi forming on lesions without rupture (plaque erosion), most often on pathological intimal thickening or fibroatheromas. However, the mechanisms involved in plaque erosion remain largely unknown, although coronary spasm is suspected. The calcified nodule has been suggested as a rare cause of coronary thrombosis in highly calcified and tortious arteries in older individuals. To characterize the severity and prognosis of plaques, several terms are used. Plaque burden denotes the extent of disease, whereas plaque activity is an ambiguous term, which may refer to one of several processes that characterize progression. Plaque vulnerability describes the short-term risk of precipitating symptomatic thrombosis. In this review, we discuss mechanisms of atherosclerotic plaque initiation and progression; how plaques suddenly precipitate life-threatening thrombi; and the concepts of plaque burden, activity, and vulnerability.