Veyssier-Belot C, Cacoub P
Service de Médecine Interne, CHI Poissy-Saint Germain, France.
Cardiovasc Res. 1999 Nov;44(2):274-82. doi: 10.1016/s0008-6363(99)00230-8.
Pulmonary hypertension can occur either as primary or secondary disease following cardiac or pulmonary illnesses. In either cases, histological lung biopsies reveal vascular remodelling i.e. smooth muscle cells proliferation with medial hypertrophy, arteriolar muscularization and endothelial cell proliferation. Subsequent intimal thickening, fibrosis and in situ thrombosis, altogether lead to vaso-occlusive alterations referred to as plexiform lesions. Theories concerning the detailed physiopathology of pulmonary hypertension have focused on endothelial and smooth muscle cells' chemical factors production and response to different mediators. The endothelium produces vasoconstrictor and growth-promoting factor such as endothelin-1 (ET-1) as well as vasodilator and growth-inhibitor factors like prostacyclin and nitric oxide (NO). ET-1 has been noted in high concentrations in some clinical cases and experimental models of pulmonary hypertension, coupled with ET-1 receptors' modulation and altered endothelin converting enzyme activities, suggesting their active role in both arteriolar vasoconstriction and occlusion. Vascular thrombosis which has been noted by pathologists in pulmonary hypertension, could be related to an imbalance between thrombotic inducing factors (such as anti-phospholipid antibodies, ET-1 and thromboxane) and decreased fibrinolytic activity and antiaggregant endothelial factors (like prostacyclin, NO, thrombomodulin). The discovery of an endothelial cells' monoclonal proliferation in plexiform lesions of patients with primary pulmonary hypertension may reinforce the cellular proliferation hypothesis to understand the histopathology of this disease. In view of these new findings, the treatments available for pulmonary hypertension have been expanded from the previously employed oxygen therapy, calcium-channel blockers and anticoagulants, to intravenous prostacyclin analogues (epoprostenol) and inhaled nitric oxide.
肺动脉高压可作为原发性疾病出现，也可继发于心脏或肺部疾病。在这两种情况下，肺组织活检均显示血管重塑，即平滑肌细胞增殖伴中膜肥厚、小动脉肌化和内皮细胞增殖。随后的内膜增厚、纤维化和原位血栓形成，共同导致血管闭塞性改变，即丛状病变。关于肺动脉高压详细病理生理学的理论主要集中在内皮细胞和平滑肌细胞化学因子的产生以及对不同介质的反应。内皮细胞产生血管收缩和生长促进因子，如内皮素-1（ET-1），以及血管舒张和生长抑制因子，如前列环素和一氧化氮（NO）。在一些肺动脉高压的临床病例和实验模型中，已发现ET-1浓度较高，同时伴有ET-1受体的调节和内皮素转换酶活性的改变，这表明它们在小动脉血管收缩和闭塞中均起积极作用。病理学家在肺动脉高压中发现的血管血栓形成，可能与血栓形成诱导因子（如抗磷脂抗体、ET-1和血栓素）与纤维蛋白溶解活性降低及抗聚集内皮因子（如前列环素、NO、血栓调节蛋白）之间的失衡有关。在原发性肺动脉高压患者的丛状病变中发现内皮细胞单克隆增殖，可能会加强细胞增殖假说，以理解该疾病的组织病理学。鉴于这些新发现，肺动脉高压的现有治疗方法已从以前使用的氧疗、钙通道阻滞剂和抗凝剂，扩展到静脉注射前列环素类似物（依前列醇）和吸入一氧化氮。
