Center for Sickle Cell Disease, Howard University, Washington, DC, United States of America.
PLoS One. 2009 Nov 23;4(11):e7956. doi: 10.1371/journal.pone.0007956.
Pulmonary hypertension and left ventricular diastolic dysfunction are complications of sickle cell disease. Pulmonary hypertension is associated with hemolysis and hypoxia, but other unidentified factors are likely involved in pathogenesis as well.
Plasma concentrations of three angiogenic markers (fibroblast growth factor, platelet derived growth factor-BB [PDGF-BB], vascular endothelial growth factor [VEGF]) and seven inflammatory markers implicated in pulmonary hypertension in other settings were determined by Bio-Plex suspension array in 237 children and adolescents with sickle cell disease at steady state and 43 controls. Tricuspid regurgitation velocity (which reflects systolic pulmonary artery pressure), mitral valve E/Edti ratio (which reflects left ventricular diastolic dysfunction), and a hemolytic component derived from four markers of hemolysis and hemoglobin oxygen saturation were also determined.
Plasma concentrations of interleukin-8, interleukin-10 and VEGF were elevated in the patients with sickle cell disease compared to controls (P<or=0.003). By logistic regression, greater values for PDGF-BB (P = 0.009), interleukin-6 (P = 0.019) and the hemolytic component (P = 0.026) were independently associated with increased odds of elevated tricuspid regurgitation velocity while higher VEGF concentrations were associated with decreased odds (P = 0.005) among the patients with sickle cell disease. These findings, which are consistent with reports that PDGF-BB stimulates and VEGF inhibits vascular smooth muscle cell proliferation, did not apply to E/Etdi.
Circulating concentrations of angiogenic and pro-Inflammatory markers are altered in sickle cell disease children and adolescents with elevated tricuspid regurgitation velocity, a subgroup that may be at risk for developing worsening pulmonary hypertension. Further studies to understand the molecular changes in these children are indicated.
肺动脉高压和左心室舒张功能障碍是镰状细胞病的并发症。肺动脉高压与溶血和缺氧有关，但其他未确定的因素也可能参与发病机制。
通过 Bio-Plex 悬浮阵列技术，在 237 名稳定期镰状细胞病儿童和青少年以及 43 名对照者中，测定了三种血管生成标志物（成纤维细胞生长因子、血小板衍生生长因子-BB[PDGF-BB]、血管内皮生长因子[VEGF]）和七种炎症标志物的血浆浓度，这些标志物在其他情况下与肺动脉高压有关。还测定了三尖瓣反流速度（反映收缩期肺动脉压）、二尖瓣 E/Edti 比值（反映左心室舒张功能障碍）以及源自四项溶血标志物和血红蛋白氧饱和度的溶血成分。
与对照组相比，镰状细胞病患者的白细胞介素-8、白细胞介素-10 和 VEGF 的血浆浓度升高（P<0.003）。通过逻辑回归分析，PDGF-BB（P=0.009）、白细胞介素-6（P=0.019）和溶血成分（P=0.026）的值越大，三尖瓣反流速度升高的几率越大，而 VEGF 浓度越高，则镰状细胞病患者的几率越低（P=0.005）。这些发现与 PDGF-BB 刺激和 VEGF 抑制血管平滑肌细胞增殖的报告一致，但不适用于 E/Etdi。
循环中血管生成和促炎标志物的浓度在患有三尖瓣反流速度升高的镰状细胞病儿童和青少年中发生改变，这群患者可能有发生肺动脉高压恶化的风险。需要进一步的研究来了解这些儿童的分子变化。
