An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque?
An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque?
复制标题
DOI：
10.12688/f1000research.15994.1
复制
发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
S. Schwartz;R. Virmani;M. Majesky
中科院分区：
文献类型：
--
作者：
S. Schwartz;R. Virmani;M. Majesky
大约50年前，Earl Benditt和他的儿子John描述了动脉粥样硬化斑块的克隆性。这导致Benditt提出动脉粥样硬化病变是平滑肌肿瘤，类似于大多数妇女子宫中的平滑肌瘤。虽然克隆性的观察已经被证实了很多次，兴趣的想法，动脉粥样硬化可能是一种形式的肿瘤减弱，因为临床成功的治疗动脉粥样硬化，因为动物模型已经取得了很大的进展，了解脂质在斑块中积累，并可能导致斑块破裂。有四项进展使得重新考虑本迪特的观察变得重要。首先，我们现在知道克隆性是正常组织发育的一种特性。第二，在血管壁中也是如此，我们现在知道，血管壁中克隆斑块的形成是构成动脉图尼卡中膜的平滑肌细胞发育的一部分。第三，我们知道内膜，人类动脉粥样硬化病变发展的“土壤”，在脂肪病变出现之前就已经发展。第四，虽然构成内膜的细胞被称为“平滑肌细胞”，但我们对细胞类型没有明确的定义，也不知道最初的积累是否是克隆的。因此，Benditt的假设需要重新审视，因为我们如何定义平滑肌细胞以及构成所有动脉壁肌层的细胞的完全不同的发育起源。最后，既然病变的克隆性是真实的，那么明显的问题是这些人类肿瘤是否先于动脉粥样硬化的发展，克隆是如何发展的，什么样的细胞类型产生了克隆，克隆以什么方式为动脉粥样硬化的发展和自然史提供了土壤？
Almost 50 years ago, Earl Benditt and his son John described the clonality of the atherosclerotic plaque. This led Benditt to propose that the atherosclerotic lesion was a smooth muscle neoplasm, similar to the leiomyomata seen in the uterus of most women. Although the observation of clonality has been confirmed many times, interest in the idea that atherosclerosis might be a form of neoplasia waned because of the clinical success of treatments for hyperlipemia and because animal models have made great progress in understanding how lipid accumulates in the plaque and may lead to plaque rupture. Four advances have made it important to reconsider Benditt’s observations. First, we now know that clonality is a property of normal tissue development. Second, this is even true in the vessel wall, where we now know that formation of clonal patches in that wall is part of the development of smooth muscle cells that make up the tunica media of arteries. Third, we know that the intima, the “soil” for development of the human atherosclerotic lesion, develops before the fatty lesions appear. Fourth, while the cells comprising this intima have been called “smooth muscle cells”, we do not have a clear definition of cell type nor do we know if the initial accumulation is clonal. As a result, Benditt’s hypothesis needs to be revisited in terms of changes in how we define smooth muscle cells and the quite distinct developmental origins of the cells that comprise the muscular coats of all arterial walls. Finally, since clonality of the lesions is real, the obvious questions are do these human tumors precede the development of atherosclerosis, how do the clones develop, what cell type gives rise to the clones, and in what ways do the clones provide the soil for development and natural history of atherosclerosis?