Bushuev Vladimir I, Miasnikova Galina Y, Sergueeva Adelina I, Polyakova Lydia A, Okhotin Daniel, Gaskin Peter R, Debebe Zufan, Nekhai Sergei, Castro Oswaldo L, Prchal Josef T, Gordeuk Victor R
Chuvash Republic Cardiac Center, Cheboksary, Chuvashia, Russia.
Haematologica. 2006 Jun;91(6):744-9.
Endothelin-1 has been associated with development of hypoxia-related pulmonary hypertension and vascular endothelial growth factor (VEGF) with protection from this complication. In Chuvash polycythemia, homozygous germline von Hippel-Lindau (VHL) 598C->T leads to up-regulation during normoxia of hypoxia inducible factor-1a and several hypoxia-controlled genes including erythropoietin and VEGF. We postulated that endothelin-1 and pulmonary artery pressure may be elevated in Chuvash polycythemia.
Systolic pulmonary artery blood pressure was estimated by Doppler echocardiography and plasma concentrations of endothelin-1, VEGF and erythropoietin were determined in 14 patients with Chuvash polycythemia and 14 controls. Results. Plasma endothelin-1 (p=0.010), VEGF (p=0.022) and erythropoietin (p<0.0005) concentrations and Doppler-estimated systolic pulmonary artery pressures (p<0.0005) were higher in the patients while systolic systemic blood pressures were lower (p=0.001). Five (36%) patients and no controls had mild pulmonary hypertension defined as systolic pulmonary artery pressure (c) 35 mmHg. Among the patients with Chuvash polycythemia, the trends of association of estimated pulmonary artery pressure with plasma concentrations of endothelin-1 (R = +0.236), VEGF (R = -0.389) and erythropoietin (R = +0.220) were not statistically significant.
Estimated systolic pulmonary artery pressure and plasma concentrations of endothelin-1 and VEGF are increased in patients with Chuvash polycythemia patients. The lack of significant associations of estimated systolic pulmonary artery pressure with plasma endothelin-1 and VEGF levels could conceivably be due to the small sample size. Further studies are indicated, especially in view of the reported efficacy of endothelin-1 receptor blockers in treating hypoxia-associated pulmonary hypertension.
内皮素 -1 与缺氧相关的肺动脉高压的发生有关，而血管内皮生长因子（VEGF）则具有预防该并发症的作用。在楚瓦什红细胞增多症中，纯合子种系冯·希佩尔 - 林道（VHL）598C→T 导致缺氧诱导因子 -1α以及包括促红细胞生成素和 VEGF 在内的多个缺氧调控基因在常氧状态下上调。我们推测楚瓦什红细胞增多症患者的内皮素 -1 和肺动脉压力可能会升高。
通过多普勒超声心动图估算收缩期肺动脉血压，并测定 14 例楚瓦什红细胞增多症患者和 14 例对照者血浆中内皮素 -1、VEGF 和促红细胞生成素的浓度。结果：患者的血浆内皮素 -1（p = 0.010）、VEGF（p = 0.022）和促红细胞生成素（p < 0.0005）浓度以及多普勒估算的收缩期肺动脉血压（p < 0.0005）较高，而收缩期体循环血压较低（p = 0.001）。5 例（36%）患者存在轻度肺动脉高压（定义为收缩期肺动脉血压≥35 mmHg），而对照组无此情况。在楚瓦什红细胞增多症患者中，估算的肺动脉压力与血浆内皮素 -1（R = +0.236）、VEGF（R = -0.389）和促红细胞生成素（R = +0.220）浓度之间的关联趋势无统计学意义。
楚瓦什红细胞增多症患者的估算收缩期肺动脉血压以及血浆内皮素 -1 和 VEGF 浓度升高。估算的收缩期肺动脉血压与血浆内皮素 -1 和 VEGF 水平缺乏显著关联可能是由于样本量较小所致。鉴于内皮素 -1 受体阻滞剂在治疗缺氧相关肺动脉高压方面已报道的疗效，有必要进行进一步研究。
