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人类动脉粥样硬化斑块单克隆起源的证据。

Evidence for a monoclonal origin of human atherosclerotic plaques.

作者信息

Benditt E P, Benditt J M

出版信息

Proc Natl Acad Sci U S A. 1973 Jun;70(6):1753-6. doi: 10.1073/pnas.70.6.1753.

DOI:10.1073/pnas.70.6.1753
PMID:4515934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC433588/
Abstract

The main cellular elements of atherosclerotic plaques are smooth muscle cells. Because these plaques differ from their precursors in the underlying artery wall in several ways, we have asked the question: Are human atherosclerotic plaques polyclonal or monoclonal in their origin? The X-linked glucose-6-phosphate dehydrogenase (EC 1.1.1.49) in heterozygotic females has been used to obtain an answer. 30 Plaques of different degrees of complexity and 59 samples of normal aorta and iliac artery walls from four females, 25-79 years old, were investigated. The data show that fibrous caps even of relatively large atheromatous plaques, 0.5 cm or greater in diameter, are composed of cells that produce solely or predominantly one enzyme type, whereas samples of artery wall media and intima as small as 0.1 mm(3) are regularly composed of a mixture of cell types. If plaques were a response to injury akin to a healing wound, a reaction to a growth stimulant, or formed due to an organization of a mural thrombus, they would be expected to be polyclonal. Hence, the results imply that atherosclerotic plaques in human beings arise by another mechanism. The mechanism compatible with the monoclonal nature of atherosclerotic plaques is mutation, and the likely causes are chemical mutagens or viruses.

摘要

动脉粥样硬化斑块的主要细胞成分是平滑肌细胞。由于这些斑块在几个方面与其在动脉壁下层的前身不同,我们提出了一个问题:人类动脉粥样硬化斑块在起源上是多克隆的还是单克隆的?已利用杂合子女性体内的X连锁葡萄糖-6-磷酸脱氢酶(EC 1.1.1.49)来寻找答案。对4名年龄在25至79岁女性的30个不同复杂程度的斑块以及59个正常主动脉和髂动脉壁样本进行了研究。数据表明,即使是直径0.5厘米或更大的相对较大的动脉粥样硬化斑块的纤维帽,也是由仅产生或主要产生一种酶类型的细胞组成,而小至0.1立方毫米的动脉壁中层和内膜样本通常由多种细胞类型混合组成。如果斑块是对类似于愈合伤口的损伤的反应、对生长刺激物的反应或由于壁血栓机化形成的,那么它们预计会是多克隆的。因此,结果表明人类动脉粥样硬化斑块是通过另一种机制形成的。与动脉粥样硬化斑块单克隆性质相符的机制是突变,可能的原因是化学诱变剂或病毒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a241/433588/e912ce549e1e/pnas00069-0135-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a241/433588/e912ce549e1e/pnas00069-0135-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a241/433588/e912ce549e1e/pnas00069-0135-a.jpg

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1
Evidence for a monoclonal origin of human atherosclerotic plaques.人类动脉粥样硬化斑块单克隆起源的证据。
Proc Natl Acad Sci U S A. 1973 Jun;70(6):1753-6. doi: 10.1073/pnas.70.6.1753.
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本文引用的文献

1
The applications of genetic mosaicism to developmental problems.基因嵌合现象在发育问题中的应用。
Annu Rev Genet. 1971;5:143-62. doi: 10.1146/annurev.ge.05.120171.001043.
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Glucose-6-phosphate dehydrogenase mosaicism: utilization as a cell marker in the study of leiomyomas.葡萄糖-6-磷酸脱氢酶嵌合体:在平滑肌瘤研究中作为细胞标志物的应用
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Glucose-6-phosphate dehydrogenase mosaicism: ito;ozatopm om tje study of hair follicle variegation.葡萄糖-6-磷酸脱氢酶嵌合体:对毛囊斑驳现象的伊藤;奥扎托普姆研究 (这段英文原文似乎存在拼写错误,翻译可能不太准确,需进一步确认原文准确内容)
动脉粥样硬化斑块的突变图谱揭示了大量克隆细胞群体。
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Manifestations of human atherosclerosis across vascular beds.人类动脉粥样硬化在不同血管床的表现。
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Insights from Murine Studies on the Site Specificity of Atherosclerosis.从鼠类研究看动脉粥样硬化的病变部位特异性。
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Vascular Damage and Repair - Are Small-Diameter Vascular Grafts Still the "Holy Grail" of Tissue Engineering?血管损伤与修复——小直径血管移植物仍是组织工程学的“圣杯”吗?
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Atherosclerosis Is a Smooth Muscle Cell-Driven Tumor-Like Disease.动脉粥样硬化是一种平滑肌细胞驱动的肿瘤样疾病。
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Clonal Expansion in Cardiovascular Pathology.心血管病理学中的克隆性扩增
JACC Basic Transl Sci. 2023 Jul 19;9(1):120-144. doi: 10.1016/j.jacbts.2023.04.008. eCollection 2024 Jan.
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Role of vascular smooth muscle cell clonality in atherosclerosis.血管平滑肌细胞克隆性在动脉粥样硬化中的作用。
Front Cardiovasc Med. 2023 Nov 28;10:1273596. doi: 10.3389/fcvm.2023.1273596. eCollection 2023.
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Mechanistic target of rapamycin in regulating macrophage function in inflammatory cardiovascular diseases.雷帕霉素靶蛋白在调节炎症性心血管疾病中巨噬细胞功能中的作用机制。
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Alterations in population dynamics of arterial smooth muscle cells during atherogenesis. I. Activation of interphase cells in cholesterol-fed swine prior to gross atherosclerosis demonstrated by "postpulse-salvage labeling".
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The ultrastructure of spontaneous and experimentally induced arterial lesions. 3. The cholesterol-induced lesions and the effect of a cholesterol and oil diet on the preexisting spontaneous plaque in the chicken aorta.自发性和实验性诱导动脉病变的超微结构。3. 胆固醇诱导的病变以及胆固醇和油类饮食对鸡主动脉中预先存在的自发性斑块的影响。
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The ultrastructure of spontaneous and experimentally induced arterial lesions. II. The spontaneous plaque in the chicken.自发性和实验性诱导动脉病变的超微结构。II. 鸡的自发性斑块
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