血管生成素-1和血管生成素-2在先天性心脏病肺动脉高压形成中的变化和意义

Changes and significance of angiopoietin-1 and angiopoietin-2 in congenital heart disease-induced pulmonary arterial hypertension

目的研究血管生成素-1(angiopoietin-1)和血管生成素-2(angiopoietin-2)在先天性心脏病肺动脉高压形成过程中的变化和意义。方法 42例先天性心脏病手术患者根据术中肺动脉测压结果,分为先心病不伴有肺动脉高压组(16例),先心病伴轻度肺动脉高压组(15例)和先心病伴中重度肺动脉高压组(11例)。8例因肺大疱行肺叶楔形切除术的患者为正常对照组。对患者肺组织内angiopoietin-1、angiopoietin-2、Tie2和激活型caspase-3进行检测。结果先心病伴肺动脉高压患者肺微细动脉内膜内皮细胞肥大增生。先心病伴轻度肺动脉高压组和先心病伴中重度肺动脉高压组angiopoietin-1和Tie2的表达逐渐升高。肺动脉高压患者肺组织内Tie2的磷酸化也逐渐增加,但激活型caspase-3却明显降低。结论内皮细胞凋亡减少可能是先心病肺动脉高压形成中一个重要的病理机制。angiopoietin-1/Tie2系统可能通过抑制内皮细胞凋亡,促进体-肺分流肺动脉高压的形成。然而在这个过程中angiopoietin-2可能并不起明显的作用。

[Objective] To elucidate possible roles of angiopoietin-1 （Ang-1） and angiopoietin-2 （Ang-2） in the development of congenital heart disease-induced pulmonary arterial hypertension （PAH）. [ Methods ] Forty-two pa- tients with congenital heart disease （CHD） who underwent cardiac surgery were enrolled in the study. Patients were separated into 3 groups as CHD without PAH （16 patients）, CHD with mild PAH （15 patients） and CHD with moderate and severe PAH （11 patients） on the evaluation of pulmonary pressure. Eight patients with normal lung histology who underwent wedge resection of the lung because of pulmonary bullae were studied as control patients. Ang-1, Ang-2, Tie2, phosphorylated Tie2 and activated caspase-3 expressions in lung specimens were investigated. [Results ] Lung histological analysis in CHD with PAH groups exhibited endothelial cell hypertrophy and proliferation in the intima of pulmonary arterioles. The expression of Ang-1 and Tie2 was upregulated gradually in CHD with mild PAH group and CHD with moderate and severe PAH group. The phosphorylation of Tie2 was also increased gradually in the lungs of patients with PAH. But activated caspase-3 was severely reduced in the lungs of patients with PAH. [ Conclusions ] Decreased apoptosis of endothelial cells may be an essential part of the pathogenesis of congenital heart disease-induced pulmonary hypertension. Ang-1/Tie2 system may protect the pulmonary endothelium against apoptosis and promote the development of pulmonary arterial hypertension, while Ang-2 may have no significant effect on this process.