Megalou Aikaterini J, Glava Chryssoula, Oikonomidis Dimitrios L, Vilaeti Agapi, Agelaki Maria G, Baltogiannis Giannis G, Papalois Apostolos, Vlahos Antonios P, Kolettis Theofilos M
Int J Clin Exp Med. 2010 Oct 23;3(4):332-40.
The role of transforming growth factor-β in the pathogenesis of pulmonary arterial hypertension is unclear. We examined the effects of T9429, an antibody against transforming growth factor-β receptors, on hemodynamic, histological and functional parameters in the rat model of monocrotaline-induced pulmonary hypertension. One week after monocrotaline injection (60 mg/kg) in 28 Wistar rats, T9429 (0.1mg/kg daily) was administered intraperito-neally in 19 rats (268±10g) via an osmotic mini-pump for 7 days. One week thereafter, right ventricular systolic pressure, pulmonary vascular remodeling and exercise tolerance were evaluated. Compared to the monocrotaline group (25.5±1.9mmHg), right ventricular systolic pressure was lower (p=0.0014) in the monocrotaline+antibody group (18.4±0.8mmHg). This was translated into attenuated right ventricular hypertrophy (p=0.0063) and longer (p=0.0155) exercise duration (2.08±0.29min versus 6.19±1.02min). Pulmonary arterial wall thickness (in vessels 50 -200μm) was comparable between the two groups, but the monocrotaline+antibody group displayed lower number (p<0.0001) of pre-capillary arterioles (<50μm, in 20 randomly selected fields) with a muscularized media (23.33±3.15 versus 6.64±0.75). Our results suggest that transforming growth factor-β receptor blockade improves vascular remodeling and attenuates pulmonary hypertension, a finding with potential therapeutic implications.
转化生长因子-β在肺动脉高压发病机制中的作用尚不清楚。我们研究了抗转化生长因子-β受体抗体T9429对野百合碱诱导的大鼠肺动脉高压模型的血流动力学、组织学和功能参数的影响。在28只Wistar大鼠注射野百合碱（60mg/kg）一周后，19只大鼠（体重268±10g）通过渗透微型泵腹腔注射T9429（每日0.1mg/kg），持续7天。此后一周，评估右心室收缩压、肺血管重塑和运动耐力。与野百合碱组（25.5±1.9mmHg）相比，野百合碱+抗体组的右心室收缩压较低（p=0.0014，为18.4±0.8mmHg）。这转化为右心室肥厚减轻（p=0.0063）和运动持续时间延长（p=0.0155，分别为2.08±0.29分钟和6.19±1.02分钟）。两组之间肺动脉壁厚度（50-200μm血管）相当，但野百合碱+抗体组的肌化中膜前毛细血管（<50μm，在20个随机选择的视野中）数量较少（p<0.0001，分别为23.33±3.15和6.64±0.75）。我们的结果表明，转化生长因子-β受体阻断可改善血管重塑并减轻肺动脉高压，这一发现具有潜在的治疗意义。
