1 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Am J Respir Crit Care Med. 2014 Jul 1;190(1):98-111. doi: 10.1164/rccm.201401-0037OC.
The development of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) is associated with increased morbidity.
To elucidate whether vascular remodeling in a well-characterized PH-COPD and PH-IPF patient cohort results from similar or divergent molecular changes.
Vascular remodeling of donor, PH-COPD, and PH-IPF pulmonary arteries was assessed. Laser capture microdissected pulmonary artery profiles in combination with whole genome microarrays were performed.
Pulmonary arteries from patients with COPD and IPF with PH exhibited remodeling of vascular layers and reduction of lumen area. Pathway analyses comparing normalized gene expression profiles obtained from patients with PH-IPF or PH-COPD revealed the retinol and extracellular matrix (ECM) receptor interaction to be the most perturbed processes. Within the ECM-receptor pathway, differential regulation of 5 out of the top 10 results (collagen, type III, α-1; tenascin C; collagen, type VI, α-3; thrombospondin 2; and von Willebrand factor) were verified by real-time polymerase chain reaction and immunohistochemical staining.
Despite clinical and histologic vascular remodeling in all patients with PH-COPD and PH-IPF, differential gene expression pattern was present in pulmonary artery profiles. Several genes involved in retinol metabolism and ECM receptor interaction enable discrimination of vascular remodeling in PH-IPF or PH-COPD. This suggests that pulmonary arterial remodeling in PH-COPD and PH-IPF is caused by different molecular mechanisms and may require specific therapeutic options.
特发性肺纤维化（IPF）或慢性阻塞性肺疾病（COPD）患者发生肺动脉高压（PH）与发病率增加有关。
阐明在特征明确的 PH-COPD 和 PH-IPF 患者队列中，血管重构是否源于相似或不同的分子变化。
评估供体、PH-COPD 和 PH-IPF 肺动脉的血管重构。进行激光捕获显微解剖肺动脉形态并结合全基因组微阵列。
COPD 和 IPF 合并 PH 的患者的肺动脉表现出血管层的重构和管腔面积的减少。比较 PH-IPF 或 PH-COPD 患者的归一化基因表达谱的通路分析显示视黄醇和细胞外基质（ECM）受体相互作用是受干扰最严重的过程。在 ECM-受体途径中，对 top10 结果中的 5 个（I 型胶原，α-1；腱糖蛋白 C；III 型胶原，α-3；血小板反应蛋白 2；血管性血友病因子）进行了实时聚合酶链反应和免疫组织化学染色的差异调控。
尽管所有 PH-COPD 和 PH-IPF 患者均存在临床和组织学血管重构，但肺动脉形态的基因表达模式存在差异。一些涉及视黄醇代谢和 ECM 受体相互作用的基因可区分 PH-IPF 或 PH-COPD 的血管重构。这表明 PH-COPD 和 PH-IPF 中的肺动脉重构是由不同的分子机制引起的，可能需要特定的治疗选择。
