Large-scale identification of human cerebrovascular proteins: Inter-tissue and intracerebral vascular protein diversity.
Large-scale identification of human cerebrovascular proteins: Inter-tissue and intracerebral vascular protein diversity.
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DOI：
10.1371/journal.pone.0188540
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Wang MM
中科院分区：
文献类型：
--
作者：
Lee SJ;Kwon S;Gatti JR;Korcari E;Gresser TE;Felix PC;Keep SG;Pasquale KC;Bai T;Blanchett-Anderson SA;Wu NW;Obeng-Nyarko C;Senagbe KM;Young KC;Maripudi S;Yalavarthi BC;Korcari D;Liu AY;Schaffler BC;Keep RF;Wang MM
人脑血管系统负责调节需求依赖性灌注和维持血脑屏障（BBB）。此外，人类脑血管系统的缺陷导致中风、脑内出血、血管畸形和血管性认知障碍。本研究的目的是使用人类蛋白质图谱的表达数据发现人类脑血管系统的新蛋白质，这是一个允许公众访问人体组织免疫组织化学分析的大规模项目。我们在HPA中筛选了20，158种蛋白质，并确定了346种与人脑血管相关的表达模式。独立的实验表明，这些分布中的51/52可以在不同的大脑样本中进行实验复制。一些蛋白质（40%）表现出内皮细胞（EC）富集的表达，而其他主要表达在血管平滑肌细胞（VSMC; 18%）; 39%的这些蛋白质表达在这两种细胞类型。大多数脑EC标记物是组织寡特异性的，也就是说，它们在9个器官中平均4.8个中的内皮中表达。虽然大多数在脑内皮细胞中表达的标记物存在于所有脑毛细血管中，但在每个脑样品中，仅在一小部分脑毛细血管中表达了大量标记物（21%）。在脑VSMC中发现的蛋白质中，几乎所有蛋白质也在外周VSMC和非血管平滑肌细胞（SMC）中表达。只有一种是潜在的脑特异性的：VHL（Von Hippel-Lindau肿瘤抑制因子）。HRC（富含组氨酸的钙结合蛋白）和VHL仅限于VSMC，在非血管组织如子宫或肠道中未发现。总之，我们定义了一组脑血管蛋白，这可能与了解人类脑血管系统的独特生理学和病理生理学有关。这组蛋白质定义了血管系统中器官间的分子差异，并证实了脑内血管细胞的广泛异质性。
The human cerebrovascular system is responsible for regulating demand-dependent perfusion and maintaining the blood-brain barrier (BBB). In addition, defects in the human cerebrovasculature lead to stroke, intracerebral hemorrhage, vascular malformations, and vascular cognitive impairment. The objective of this study was to discover new proteins of the human cerebrovascular system using expression data from the Human Protein Atlas, a large-scale project which allows public access to immunohistochemical analysis of human tissues. We screened 20,158 proteins in the HPA and identified 346 expression patterns correlating to blood vessels in human brain. Independent experiments showed that 51/52 of these distributions could be experimentally replicated across different brain samples. Some proteins (40%) demonstrated endothelial cell (EC)-enriched expression, while others were expressed primarily in vascular smooth muscle cells (VSMC; 18%); 39% of these proteins were expressed in both cell types. Most brain EC markers were tissue oligospecific; that is, they were expressed in endothelia in an average of 4.8 out of 9 organs examined. Although most markers expressed in endothelial cells of the brain were present in all cerebral capillaries, a significant number (21%) were expressed only in a fraction of brain capillaries within each brain sample. Among proteins found in cerebral VSMC, virtually all were also expressed in peripheral VSMC and in non-vascular smooth muscle cells (SMC). Only one was potentially brain specific: VHL (Von Hippel-Lindau tumor suppressor). HRC (histidine rich calcium binding protein) and VHL were restricted to VSMC and not found in non-vascular tissues such as uterus or gut. In conclusion, we define a set of brain vascular proteins that could be relevant to understanding the unique physiology and pathophysiology of the human cerebrovasculature. This set of proteins defines inter-organ molecular differences in the vasculature and confirms the broad heterogeneity of vascular cells within the brain.
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影响因子：
64.5
作者：
Karaca E;Weitzer S;Pehlivan D;Shiraishi H;Gogakos T;Hanada T;Jhangiani SN;Wiszniewski W;Withers M;Campbell IM;Erdin S;Isikay S;Franco LM;Gonzaga-Jauregui C;Gambin T;Gelowani V;Hunter JV;Yesil G;Koparir E;Yilmaz S;Brown M;Briskin D;Hafner M;Morozov P;Farazi TA;Bernreuther C;Glatzel M;Trattnig S;Friske J;Kronnerwetter C;Bainbridge MN;Gezdirici A;Seven M;Muzny DM;Boerwinkle E;Ozen M;Baylor Hopkins Center for Mendelian Genomics;Clausen T;Tuschl T;Yuksel A;Hess A;Gibbs RA;Martinez J;Penninger JM;Lupski JR
通讯作者：
Lupski JR
DOI：
10.1161/atvbaha.111.232785
发表时间：
2011-10
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Long X;Slivano OJ;Cowan SL;Georger MA;Lee TH;Miano JM
通讯作者：
Miano JM
DOI：
10.1124/jpet.108.149831
发表时间：
2009-05
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Dahlin A;Royall J;Hohmann JG;Wang J
通讯作者：
Wang J
影响因子：
3.7
作者：
Daneman R;Zhou L;Agalliu D;Cahoy JD;Kaushal A;Barres BA
通讯作者：
Barres BA
影响因子：
3.7
作者：
Lerch JK;Kuo F;Motti D;Morris R;Bixby JL;Lemmon VP
通讯作者：
Lemmon VP