State University of New York Downstate Medical Center, Brooklyn, New York, USA.
Quest Diagnostics, Nichols Institute, San Juan Capistrano, California, USA.
Pulm Circ. 2013 Dec;3(4):851-5. doi: 10.1086/674763.
Pulmonary arterial hypertension (PAH) is a major complication of sickle cell disease (SCD). Low levels of apolipoprotein A1 (Apo-A1) have been implicated in the development of PAH in SCD. We speculate that lower levels of Apo-A1 are related to dysregulation of the ubiquitin-proteasome pathway (UPP). Of 36 recruited patients with SCD, 14 were found to have PAH on the basis of right heart catheterization. Levels of Apo-A1 and Apo-B, polyubiquitin, total protease, and specific and normalized activity of chymotrypsin-like, trypsin-like, and caspase-like proteases in plasma were measured. Levels of Apo-A1 were found to be lower and polyubiquitin levels were found to be significantly higher in the PAH group ([Formula: see text]) in SCD. Apo-A levels were inversely correlated with polyubiquitin levels ([Formula: see text], [Formula: see text]). These results indicate that lower levels of Apo-A1 in SCD patients with PAH are likely related to enhance degradation by UPP, potentially contributing to pulmonary vascular pathology. These findings may provide significant insight in identifying suitable therapeutic targets in these patients.
肺动脉高压（PAH）是镰状细胞病（SCD）的主要并发症。载脂蛋白 A1（Apo-A1）水平降低与 SCD 中的 PAH 发展有关。我们推测 Apo-A1 水平降低与泛素-蛋白酶体途径（UPP）失调有关。在招募的 36 名 SCD 患者中，根据右心导管检查发现 14 名患者患有 PAH。测量了血浆中 Apo-A1 和 Apo-B、多聚泛素、总蛋白酶以及糜蛋白酶样、胰蛋白酶样和半胱天冬酶样蛋白酶的特异性和归一化活性。结果发现，SCD 中的 PAH 组 Apo-A1 水平较低，多聚泛素水平显著升高（[公式：见文本]）。Apo-A 水平与多聚泛素水平呈负相关（[公式：见文本]，[公式：见文本]）。这些结果表明，PAH 患者 Apo-A1 水平降低可能与 UPP 增强降解有关，可能导致肺血管病理学。这些发现可能为确定这些患者的合适治疗靶点提供重要的见解。
