Huber Lars C, Soltermann Alex, Fischler Manuel, Gay Steffen, Weder Walter, Russi Erich W, Speich Rudolf, Ulrich Silvia
Working Group for Pulmonary Hypertension, Department for Internal Medicine, University Hospital Zurich, Zurich, Switzerland.
Open Respir Med J. 2009 May 13;3:73-8. doi: 10.2174/1874306400903010073.
Caveolin-1 is a regulator of both intracellular calcium homeostasis and endothelial nitric oxide synthase and may play a pathogenetic role in pulmonary hypertension. In the present study, we aimed to investigate the correlations between pulmonary hemodynamics and vessel morphology including the expression of Caveolin-1 in pulmonary arterioles from patients with chronic obstructive pulmonary disease (COPD) who underwent lung-volume reduction surgery. Staining and subsequent analysis was performed on paraffin-embedded lung tissue from COPD patients (n = 12). Pulmonary arteries with an external diameter of 100-500microm were analysed. Immunhistochemistry with antibodies against caveolin-1 was performed and intensity was assessed. Morphometric data were obtained by using computer-assisted imaging software. The findings were quantified and correlated to hemodynamic data obtained by right-heart catheterization. In COPD patients with pulmonary hypertension (n = 5), the expression of caveolin-1 within the medial smooth muscle cell layer was found to be increased, whereas the intimal caveolin-1 was more prominently expressed in COPD patients with normal pulmonary pressures (n = 7). The ratio between these expression patterns was positively correlated to the mean pulmonary artery pressure. Similar findings were observed for the ratio between intimal and medial thickness as well as for the expression of smooth muscle actin (SMA).Taken together, the expression of caveolin-1 within medial smooth muscle cells of pulmonary arteries in patients with COPD is associated with pulmonary hypertension. Our results thus emphasize a potential novel player in the pathogenesis of COPD-associated pulmonary hypertension.
小窝蛋白-1是细胞内钙稳态和内皮型一氧化氮合酶的调节因子,可能在肺动脉高压的发病机制中起作用。在本研究中,我们旨在调查慢性阻塞性肺疾病(COPD)患者接受肺减容手术后肺血流动力学与血管形态之间的相关性,包括肺小动脉中小窝蛋白-1的表达。对12例COPD患者石蜡包埋的肺组织进行染色及后续分析。分析外径为100 - 500微米的肺动脉。用抗小窝蛋白-1抗体进行免疫组织化学染色并评估强度。通过计算机辅助成像软件获取形态学数据。对结果进行量化,并与右心导管检查获得的血流动力学数据相关联。在患有肺动脉高压的COPD患者(n = 5)中,发现中膜平滑肌细胞层内小窝蛋白-1的表达增加,而内膜小窝蛋白-1在肺压力正常的COPD患者(n = 7)中表达更显著。这些表达模式之间的比率与平均肺动脉压呈正相关。在内膜与中膜厚度之比以及平滑肌肌动蛋白(SMA)的表达方面也观察到类似结果。综上所述,COPD患者肺动脉中膜平滑肌细胞内小窝蛋白-1的表达与肺动脉高压相关。因此,我们的结果强调了COPD相关肺动脉高压发病机制中一个潜在的新因素。