Rabinovitch M, Andrew M, Thom H, Trusler G A, Williams W G, Rowe R D, Olley P M
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Circulation. 1987 Nov;76(5):1043-52. doi: 10.1161/01.cir.76.5.1043.
In patients with pulmonary hypertension associated with congenital heart defects, ultrastructural abnormalities are observed in endothelial cells, which suggest heightened metabolic function. If endothelial production of the von Willebrand factor (vWF) is increased, this may be associated with abnormal interactions with platelets leading to worsening of the pulmonary hypertension. We therefore evaluated vWF in 30 patients with pulmonary hypertension (25 with congenital heart defects) and in 30 individuals with normal pulmonary arterial pressure (12 with congenital heart defects). We measured the antigenic (vWF: Ag) and biologic (VWF: rist) activity of vWF in plasma and assessed endothelial vWF: Ag directly by an immunoperoxidase stain applied to lung biopsy tissue. Because of considerable variance and small size, the group of five patients with pulmonary hypertension and without congenital heart defects were excluded from statistical analyses. Patients with pulmonary hypertension and congenital heart defects had significant higher vWF: Ag levels than individuals with normal pulmonary arterial pressure without congenital heart defects (p less than .05), whereas values in those with normal pressure and congenital heart defects were intermediate. In lung biopsy tissue available from 29 patients in this study and from 11 others we previously reported, immunostain of pulmonary arterial endothelium for vWF was intense (suggesting increased production) in 29 of 32 with pulmonary hypertension and congenital heart defects and in only one of eight with normal pulmonary arterial pressure and congenital heart defects (p less than .01). Only three patients with congenital heart defects and pulmonary hypertension and increased vWF: Ag, however, had increased vWF: rist. Compatible with this discrepancy was a loss of vWF high-molecular weight forms as determined by both crossed immunoelectrophoresis and multimeric analysis. Our results suggest that increased vWF in most patients with congenital heart defects and pulmonary hypertension is associated with increased production of a biologically deficient molecule lacking high-molecular weight forms.
在患有与先天性心脏缺陷相关的肺动脉高压的患者中，内皮细胞出现超微结构异常，这提示代谢功能增强。如果血管性血友病因子（vWF）的内皮生成增加，这可能与血小板的异常相互作用有关，从而导致肺动脉高压恶化。因此，我们评估了30例肺动脉高压患者（25例患有先天性心脏缺陷）和30例肺动脉压正常的个体（12例患有先天性心脏缺陷）的vWF。我们测量了血浆中vWF的抗原性（vWF:Ag）和生物学活性（VWF:rist），并通过应用于肺活检组织的免疫过氧化物酶染色直接评估内皮vWF:Ag。由于差异较大且样本量小，5例患有肺动脉高压且无先天性心脏缺陷的患者被排除在统计分析之外。患有肺动脉高压和先天性心脏缺陷的患者的vWF:Ag水平显著高于无先天性心脏缺陷的肺动脉压正常的个体（p<0.05），而血压正常且患有先天性心脏缺陷的个体的值处于中间水平。在本研究的29例患者以及我们之前报道的另外11例患者的肺活检组织中，32例患有肺动脉高压和先天性心脏缺陷的患者中有29例肺动脉内皮对vWF的免疫染色强烈（提示生成增加），而8例肺动脉压正常且患有先天性心脏缺陷的患者中只有1例如此（p<0.01）。然而，只有3例患有先天性心脏缺陷和肺动脉高压且vWF:Ag增加的患者的vWF:rist增加。与这种差异相符的是，通过交叉免疫电泳和多聚体分析确定，vWF高分子量形式有所缺失。我们的结果表明，大多数患有先天性心脏缺陷和肺动脉高压的患者中vWF增加与缺乏高分子量形式的生物学缺陷分子的生成增加有关。
