[Analysis of angiogenesis related proteins and its implication in type-2 hereditary hemorrhagic telangiectasia].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Peng
Hong-Lin
HL
Division of Hematology, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
Hu
Guo-Yu
GY
Zhang
Guang-Sen
GS
Gong
Fan-Jie
FJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D002675:Child, Preschool; D005260:Female; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000097:blood*; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000097:blood*; D016212:Transforming Growth Factor beta / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha