Vascular disease in COPD: systemic and pulmonary expression of PARC (Pulmonary and Activation-Regulated Chemokine)

Introduction. The role of Pulmonary and Activation-Regulated Chemokine (PARC) in the physiopathology of Chronic Obstructive Pulmonary Disease (COPD) is not fully understood. The aim of the present study is to analyze the expression of PARC
in lung tissue and its relationship with the vascular remodeling of the systemic and pulmonary arteries of COPD subjects.

Methods. To achieve this objective, protein and gene expression experiments, together with ELISA assays, were performed on the lung tissue, intercostal arteries and serum samples from COPD patients, non-obstructed smokers (NOS) and
never-smokers (NS).

Results. A total of 57 subjects were included in the analysis (23 COPD, 18 NOS and 16 NS). In the comparisons between groups, a significantly increased lung protein expression of PARC was observed in the COPD group compared to the NOS
group (1.96±0.22 vs. 1.29±0.27, P-adjusted=0.038). PARC was located predominantly in the smooth muscle cells of the remodeled pulmonary muscular arteries and the macrophage-rich area of the alveolar parenchyma. No differences were detected in PARC gene expression analyses. The protein
content of PARC in the intercostal arteries were similar between groups, though little remodeling was observed in these arteries. Circulating levels of PARC were numerically higher in patients with COPD compared to NOS and NS.

Conclusion. The results of the present study suggest an increased lung protein expression of PARC in COPD subjects. This protein was mainly localized in the smooth muscle cells of the pulmonary muscular arteries and was associated with the severity of intimal thickening, indicating its possible role in this remodeling process.

引言。肺脏与激活调节趋化因子（Pulmonary and Activation-Regulated Chemokine, PARC）在慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease, COPD）的病理生理过程中的作用尚未完全阐明。本研究旨在分析PARC在肺组织中的表达情况，及其与慢性阻塞性肺疾病患者体循环动脉与肺动脉血管重构的关联。

方法。为达成上述研究目标，本研究对慢性阻塞性肺疾病患者、非阻塞性吸烟者（non-obstructed smokers, NOS）以及从未吸烟者（never-smokers, NS）的肺组织、肋间动脉与血清样本开展了蛋白质与基因表达实验，并同步进行了酶联免疫吸附测定（enzyme-linked immunosorbent assay, ELISA）。

结果。本研究共纳入57名受试者（23名慢性阻塞性肺疾病患者、18名非阻塞性吸烟者及16名从未吸烟者）。组间比较结果显示，与非阻塞性吸烟者组相比，慢性阻塞性肺疾病组患者的肺组织PARC蛋白表达水平显著升高（1.96±0.22 vs. 1.29±0.27，校正后P值=0.038）。PARC主要定位于发生重构的肺肌性动脉的平滑肌细胞以及肺泡实质内富含巨噬细胞的区域。PARC的基因表达水平未检测到组间差异。各组肋间动脉中PARC的蛋白含量无明显差异，且此类动脉未观察到明显重构。慢性阻塞性肺疾病患者的循环PARC水平数值上高于非阻塞性吸烟者与从未吸烟者组。

结论。本研究结果提示，慢性阻塞性肺疾病患者的肺组织PARC蛋白表达水平升高。该蛋白主要定位于肺肌性动脉的平滑肌细胞，且与内膜增厚的严重程度相关，表明其可能参与了该血管重构过程。