Peng Hong-Lin, Hu Guo-Yu, Zhang Guang-Sen, Gong Fan-Jie
Division of Hematology, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
Zhonghua Xue Ye Xue Za Zhi. 2006 Sep;27(9):616-20.
To detect the level of transforming growth factor-beta1 (TGF-beta1), TGF-beta2, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor-alpha (PDGFRalpha) in plasma and peripheral blood leukocytes in a hereditary hemorrhagic telangiectasia type 2 (HHT-2) family, and explore the implication of angiogenesis related proteins in HHT-2 pathogenesis.
The diagnosis of the HHT-2 patient was based on clinical features and further confirmed by determining a C1231T mutation of activin receptor-like kinase 1 (ALK1) gene. Five other new members in this family were evaluated with ALK1 gene screening and clinical manifestation. Plasma level of TGF-beta1, TGF-beta2 or VEGF was measured by ELISA, and the expression of PDGFRalpha,TGF-beta1, and VEGF in peripheral blood leukocytes by flow cytometry combined with direct or indirect immunofluorescence.
No C1231T mutation was detected in exon 8 of ALK1 gene in the 5 new members. Plasma TGF-beta1 and TGF-beta2 concentration in 3 affected HHT case was (16 954 +/- 3 709) ng/L and (11 548 +/- 2 611) ng/L, respectively, compared with that of normal control, the difference was not significant (P > 0.05). VEGF concentration in the 3 HHT patients, 6 unaffected family members and 6 normal controls was (179.2 +/- 22.0) microg/L, (149.8 +/- 22.7) microg/L and (132.9 +/- 21.0) microg/ L, respectively. Plasma VEGF level in HHT patients was significantly higher than that in normal subjects (P < 0.025). Peripheral leukocyte PDGFRalpha and VEGF in HHT patients and unaffected family members were markedly higher than that of normal control (P < 0.05 and P < 0.02), while TGF-beta1 distribution was similar in HHT patients and normal subjects.
Compared with normal controls there is no difference in plasma TGF-beta1 concentration on peripheral leukocytes of HHT patients. Plasma VEGF concentration or leukocytes VEGF expression in HHT is significantly higher than that of normal subjects. Leukocytes PDGFRalpha expression in HHT is significantly higher than that of normal control. These changes may be associated with a compensable mechanism in HHT.
检测2型遗传性出血性毛细血管扩张症（HHT - 2）家系血浆及外周血白细胞中转化生长因子 - β1（TGF - β1）、TGF - β2、血管内皮生长因子（VEGF）和血小板衍生生长因子受体 - α（PDGFRα）的水平，探讨血管生成相关蛋白在HHT - 2发病机制中的意义。
HHT - 2患者的诊断基于临床特征，并通过检测激活素受体样激酶1（ALK1）基因的C1231T突变进一步确诊。对该家系中的其他5名新成员进行ALK1基因筛查和临床表现评估。采用酶联免疫吸附测定法（ELISA）检测血浆中TGF - β1、TGF - β2或VEGF水平，采用流式细胞术结合直接或间接免疫荧光法检测外周血白细胞中PDGFRα、TGF - β1和VEGF的表达。
5名新成员的ALK1基因第8外显子未检测到C1231T突变。3例HHT患者血浆TGF - β1和TGF - β2浓度分别为（16 954±3 709）ng/L和（11 548±2 611）ng/L，与正常对照组相比，差异无统计学意义（P>0.05）。3例HHT患者、6例未患病家庭成员和6例正常对照者的VEGF浓度分别为（179.2±22.0）μg/L、（149.8±22.7）μg/L和（132.9±21.0）μg/L。HHT患者血浆VEGF水平显著高于正常受试者（P<0.025）。HHT患者和未患病家庭成员外周血白细胞中的PDGFRα和VEGF明显高于正常对照组（P<0.05和P<0.02），而HHT患者和正常受试者的TGF - β1分布相似。
与正常对照组相比，HHT患者外周血白细胞中血浆TGF - β1浓度无差异。HHT患者血浆VEGF浓度或白细胞VEGF表达显著高于正常受试者。HHT患者白细胞中PDGFRα表达显著高于正常对照组。这些变化可能与HHT中的一种代偿机制有关。
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