Mast Cell Inhibition Improves Pulmonary Vascular Remodeling in Pulmonary Hypertension
Mast Cell Inhibition Improves Pulmonary Vascular Remodeling in Pulmonary Hypertension
复制标题
DOI：
10.1378/chest.11-0663
复制
发表时间：
2012-03-01
期刊：
影响因子：
9.6
通讯作者：
Berger, Rolf M. F.
中科院分区：
文献类型：
--
作者：
Bartelds, Beatrijs;van Loon, Rosa Laura E.;Berger, Rolf M. F.
背景：肺动脉高压（PAH）是一种进行性血管增生性疾病，具有较高的发病率和死亡率。虽然组织病理学描述良好，但其发病机制在很大程度上是未知的。我们以前确定了肥大细胞及其标记物在大鼠模型中的流动相关PAH的存在增加。本研究的目的是测试肥大细胞的稳定性对肺血管重塑的影响，在实验性PAH.Methods：大鼠与流量相关的PAR创建野百合碱和一个腔静脉分流处理与肥大细胞稳定剂crologyn，并与未处理的大鼠和对照组大鼠进行比较。此外，我们用肥大细胞蛋白酶之一的糜酶抑制剂（TY-51469）治疗了一组PAR大鼠。结果：PAR大鼠肥大细胞、糜酶活性和炎性标志物增加。肥大细胞稳定剂治疗减弱肺血管重构，但不影响血流动力学。一个较低的肺糜酶活性与更有利的肺血管重塑以及血流动力学和炎症markers.Conclusions：我们表明，在大鼠肺动脉高压，肥大细胞稳定衰减肺血管重塑和较低的糜酶活性与更有利的血流动力学和肺血管重塑。本实验研究的结果支持使用肥大细胞稳定剂（一组已获准临床使用的药物）进行抗肿瘤治疗以减缓PAH疾病进展的概念。胸部2012; 141（3）：651-660
Background: Pulmonary arterial hypertension (PAH) is a progressive angioproliferative disease with high morbidity and mortality. Although the histopathology is well described, its pathogenesis is largely unknown. We previously identified the increased presence of mast cells and their markers in a rat model of flow-associated PAH. The aim of this study was to test the effect of mast cell stabilization on pulmonary vascular remodeling in experimental PAH.Methods: Rats with flow-associated PAR created by monocrotaline and an aorto-caval shunt were treated with the mast cell stabilizer cromolyn and compared with untreated rats and control rats. Further, we treated a group of rats with PAR with an inhibitor (TY-51469) of chymase, one of the mast cell proteases. The effects on pulmonary vascular remodeling and hemodynamics were assessed.Results: Rats with PAR had increased mast cells, chymase activity, and inflammatory markers. Treatment with mast cell stabilizer attenuated pulmonary vascular remodeling but not hemodynamics. A lower pulmonary chymase activity correlated with more favorable pulmonary vascular remodeling as well as hemodynamics and inflammatory markers.Conclusions: We showed in rats with PAH that mast cell stabilization attenuated pulmonary vascular remodeling and that a lower chymase activity correlated with more favorable hemodynamics and pulmonary vascular remodeling. The results of this experimental study support the concept of the use of antiinflammatory therapy by mast cell stabilizers, a group of drugs already licensed for clinical use, to attenuate disease progression in PAH. CHEST 2012; 141(3):651-660