Shanxi Medical University, Taiyuan, China.
Inhal Toxicol. 2012 Jul;24(8):468-75. doi: 10.3109/08958378.2012.688885.
Pulmonary artery hypertension (PAH) is a severe disease characterized with progressive increase of pulmonary vascular resistance that finally causes right ventricular failure and premature death. Cigarette smoke (CS) is a major factor of Chronic Obstructive Pulmonary Disease (COPD) that can lead to PAH. However, the mechanism of CS-induced PAH is poorly understood. Mounting evidence supports that pulmonary vascular remodeling play an important role in the development of PAH. PDGF signaling has been demonstrated to be a major mediator of vascular remodeling implicated in PAH. However, the association of PDGF signaling with CS-induced PAH has not been documented. In this study, we investigated CS-induced PAH in rats and the expression of platelet derived growth factor (PDGF) and PDGF receptor (PDGFR) in pulmonary artery. Forty male rats were randomly divided into control group and three experimental groups that were exposed to CS for 1, 2, and 3 months, respectively. CS significantly increased right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI). Histology staining demonstrated that CS significantly increased the thickness of pulmonary artery wall and collagen deposition. The expression of PDGF isoform B (PDGF-B) and PDGF receptor beta (PDGFRβ) were significantly increased at both protein and mRNA levels in pulmonary artery of rats with CS exposure. Furthermore, Cigarette smoke extract (CSE) significantly increased rat pulmonary artery smooth muscle cell (PASMC) proliferation, which was inhibited by PDGFR inhibitor Imatinib. Thus, our data suggest PDGF signaling is implicated in CS-induced PAH.
肺动脉高压（PAH）是一种严重的疾病，其特征是肺血管阻力逐渐增加，最终导致右心衰竭和过早死亡。香烟烟雾（CS）是慢性阻塞性肺疾病（COPD）的主要因素，可导致 PAH。然而，CS 引起 PAH 的机制尚不清楚。越来越多的证据表明，肺血管重构在 PAH 的发展中起着重要作用。PDGF 信号已被证明是血管重构的主要介质，与 PAH 有关。然而，PDGF 信号与 CS 诱导的 PAH 之间的关联尚未有文献记载。在这项研究中，我们研究了 CS 诱导的大鼠 PAH 以及血小板衍生生长因子（PDGF）和 PDGF 受体（PDGFR）在肺动脉中的表达。40 只雄性大鼠被随机分为对照组和三个实验组，分别暴露于 CS 1、2 和 3 个月。CS 显著增加了右心室收缩压（RVSP）和右心室肥厚指数（RVHI）。组织学染色表明 CS 显著增加了肺动脉壁的厚度和胶原沉积。CS 暴露大鼠肺动脉中 PDGF 同种型 B（PDGF-B）和 PDGF 受体β（PDGFRβ）的表达在蛋白和 mRNA 水平均显著增加。此外，香烟烟雾提取物（CSE）显著增加了大鼠肺动脉平滑肌细胞（PASMC）的增殖，而 PDGFR 抑制剂伊马替尼则抑制了这一增殖。因此，我们的数据表明 PDGF 信号参与了 CS 诱导的 PAH。
