Redistribution of Mature Smooth Muscle Markers in Brain Arteries in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.
Redistribution of Mature Smooth Muscle Markers in Brain Arteries in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.
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DOI：
10.1007/s12975-018-0643-x
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发表时间：
2018-06-22
影响因子：
6.9
通讯作者：
Wang MM
中科院分区：
文献类型：
--
作者：
Gatti JR;Zhang X;Korcari E;Lee SJ;Greenstone N;Dean JG;Maripudi S;Wang MM
血管平滑肌细胞（SMC）在CADASIL中经历一系列戏剧性的变化，CADASIL是血管性痴呆和中风的最常见遗传原因。NOTCH 3蛋白在CADASIL早期积累和聚集，随后是脑动脉中膜成熟SMC的丢失和显著的内膜增殖。在外周动脉疾病中观察到类似的内膜增厚，其特征在于病理性内膜细胞，包括增殖、去分化、缺乏SMC标记物的平滑肌样细胞。有限的研究已经进行了调查的分化状态和定位的SMCs在脑血管疾病。因此，我们研究了一组具有遗传特征的北美CADASIL脑中表达SMC标志物的细胞的分布。我们在9例经遗传学验证的CADASIL病例中定量了这些标记物的脑RNA丰度，发现与年龄匹配的对照组相比，CADASIL脑中几种成熟SMC标记物的mRNA表达增加。免疫组织化学研究和原位杂交定位的mRNA显示的损失SMC从动脉媒体，和SMC标记表达细胞，而不是重新分布到内膜病变动脉和周围的球囊细胞的退化媒体。我们的结论是，尽管损失中膜平滑肌细胞在患病的动脉，平滑肌标志物并没有从CADASIL脑丢失，而是，表达成熟的SMC标志物的细胞的定位发生了显着变化。
Vascular smooth muscle cells (SMCs) undergo a series of dramatic changes in CADASIL, the most common inherited cause of vascular dementia and stroke. NOTCH3 protein accumulates and aggregates early in CADASIL, followed by loss of mature SMCs from the media of brain arteries and marked intimal proliferation. Similar intimal thickening is seen in peripheral arterial disease, which features pathological intimal cells including proliferative, dedifferentiated, smooth muscle-like cells deficient in SMC markers. Limited studies have been performed to investigate the differentiation state and location of SMCs in brain vascular disorders. Thus, we investigated the distribution of cells expressing SMC markers in a group of genetically characterized, North American CADASIL brains. We quantified brain RNA abundance of these markers in nine genetically verified cases of CADASIL and found that mRNA expression for several mature SMC markers was increased in CADASIL brain compared to age-matched control. Immunohistochemical studies and in situ hybridization localization of mRNA demonstrated loss of SMCs from the arterial media, and SMC marker-expressing cells were instead redistributed into the intima of diseased arteries and around balloon cells of the degenerating media. We conclude that, despite loss of medial smooth muscle cells in diseased arteries, smooth muscle markers are not lost from CADASIL brain, but rather, the localization of cells expressing mature SMC markers changes dramatically.
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影响因子：
4
作者：
Brennan-Krohn, Thea;Salloway, Stephen;de la Monte, Suzanne M.
通讯作者：
de la Monte, Suzanne M.
影响因子：
2.9
作者：
DUBAND, JL;GIMONA, M;SMALL, JV
通讯作者：
SMALL, JV
影响因子：
20.1
作者：
Aikawa, M;Rabkin, E;Libby, P
通讯作者：
Libby, P
影响因子：
4.8
作者：
Miano, JM;Olson, EN
通讯作者：
Olson, EN
影响因子：
15.9
作者：
Regan, CP;Adam, PJ;Owens, GK
通讯作者：
Owens, GK