Endoglin expression is reduced in normal vessels but still detectable in arteriovenous malformations of patients with hereditary hemorrhagic telangiectasia type 1
Endoglin expression is reduced in normal vessels but still detectable in arteriovenous malformations of patients with hereditary hemorrhagic telangiectasia type 1
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DOI：
10.1016/s0002-9440(10)64960-7
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发表时间：
2000-03-01
影响因子：
6
通讯作者：
Letarte, M
中科院分区：
文献类型：
--
作者：
Bourdeau, A;Cymerman, U;Letarte, M
Endoglin主要在内皮细胞上表达，在遗传性出血性毛细血管扩张症1型(HHT1)中发生突变。我们报告了一例死于脑动静脉畸形(CAVM)的新生儿(家2)的组织和一名78岁的肺AVM患者(家5)手术切除的肺标本中endoglin的分析。新生儿的临床父亲发现了一种新的突变，这种突变在他的父母中是不存在的，通过定量多重聚合酶链式反应鉴定为外显子3至8的重复。相应的突变蛋白(116-kd单体)和错义突变蛋白(80-kd单体)仅被检测到为瞬时胞内物种，经Western印迹分析和免疫染色无反应。在HHT1患者外周血激活的单核细胞上，正常的endoglin(90kd单体)减少了50%。当通过免疫染色和密度测量分析时，假定新生儿肺和脑的正常血管以及与成人PAVM相邻的血管显示endoglin/PECAM-1的比率降低了50%。在CAVM和PAVM中观察到相似的比率，表明HHT1患者的所有血管原位表达endoglin减少，Avm不是由于局部endoglin丢失所致。
Endoglin is predominantly expressed on endothelium and is mutated in hereditary hemorrhagic telangiectasia (HHT) type 1 (HHT1). We report the analysis of endoglin in tissues of a newborn (family 2), who died of a cerebral arteriovenous malformation (CAVM), and in a lung specimen surgically resected from a 78-year-old patient (family 5), with a pulmonary AVM (PAVM). The clinically affected father of the newborn revealed a novel mutation that was absent in his parents and was identified as a duplication of exons 3 to 8, by quantitative multiplex polymerase chain reaction. The corresponding mutant protein (116-kd monomer) and the missense mutant protein (80-kd monomer) present in family 5 were detected only as transient intracellular species and were unreactive by Western blot analysis and immunostaining. Normal endoglin (90-kd monomer) was reduced by 50% on peripheral blood-activated monocytes of the HHT1 patients. When analyzed by immunostaining and densitometry, presumed normal blood vessels of the newborn lung and brain and vessels adjacent to the adult PAVM showed a 50% reduction in the endoglin/PECAM-1 ratio. A similar ratio was observed in the CAVM and PAVM, suggesting that all blood vessels of HHT1 patients express reduced endoglin in situ and that AVMs are not attributed to a focal loss of endoglin.