Inflammatory Reaction in Pulmonary Muscular Arteries of Patients with Mild Chronic Obstructive Pulmonary Disease

Abstract

Endothelial dysfunction and intimal thickening have been shown in pulmonary arteries (PA) of patients with mild chronic obstructive pulmonary disease (COPD). To investigate whether an inflammatory process related to tobacco smoking might be involved in the development of pulmonary vascular abnormalities in COPD, we characterized the inflammatory cell infiltrate and the endothelium-dependent relaxation in PA of 39 patients who underwent lung resection, divided into three groups: "nonsmokers" (n ϭ 7); "smokers," with normal lung function (n ϭ 12); and "COPD" (n ϭ 20). Endothelium-dependent relaxation was assessed in vitro by exposing PA rings to adenosine diphosphate (ADP). Inflammatory cell types were identified by immunohistochemistry. PA of COPD patients Structural and functional abnormalities of the pulmonary circulation are common features in the wide spectrum of chronic obstructive pulmonary disease (COPD). Dysfunction of the pulmonary endothelium, which is associated with an impaired release of endothelium-derived nitric oxide (NO), may play a critical role in the remodeling of pulmonary vessels in COPD. Endothelial dysfunction in pulmonary arteries was initially shown in end-stage COPD patients undergoing lung transplantation by Dinh-Xuan and coworkers (1). In a recent study we observed that endothelial dysfunction may also be present in pulmonary arteries of patients with mild COPD (2). However, whereas in end-stage COPD chronic severe hypoxemia may account for the impairment of the endothelial function (1), the mechanisms of such an impairment in patients with milder degrees of disease, who are not hypoxemic, are unknown.Several studies performed in lungs of patients with mild COPD have shown apparent abnormalities in the structure of the pulmonary muscular arteries, in most cases consisting of the thickening of the intimal layer (3-5). Interestingly, the intensity of the intimal thickening has been shown to correlate with the severity of the inflammatory infiltrate in small airways (5, 6), suggesting that an inflammatory process might also account for the structural abnormalities of the pulmonary artery wall. Indeed, inflammation has been shown to be involved in the pathogenesis of some forms of pulmonary hypertension (7) and also in the remodeling of systemic vessels (8). Accordingly, we hypothesized that the structural abnormalities and the endothelial dysfunction shown in pulmonary arteries of patients with mild COPD could be related to an inflammatory process.Cigarette smoking causes an inflammatory reaction in the airways of patients with COPD. Whereas in both asymptomatic smokers and patients with COPD the nature and characteristics of the inflammatory reaction in central and peripheral airways (9-14), as well as in alveolar septa (15), have been thoroughly evaluated, little is known about the degree, nature, and evolution of the inflammatory infiltrate in pulmonary arteries of COPD patients.The present study, results of which have been given in abstract form (16), was therefore addressed to inves...

Pulmonary vascular changes in asthma and COPD

“…This switch is important during resolution of vascular injury and homeostasis and appears to be regulated by different miRNAs [38,39]. Chronic inflammation and tissue hypoxia are thought to induce increased vascular growth by directly effecting the VSM cells [40] the result being muscularisation and thickening of the blood vessels [13,40,41]. Factors such as tissue damage and sheer force also prompt both EPCs and endothelial cells to transdifferentiate into VSM cells [42,43].…”

“…Patients with COPD have an increased number of infiltrating CD8 + Tlymphocytes in adventitia in pulmonary arteries [41]. It has been shown that cigarette smoke may increase the number of circulating neutrophils in the blood vessels and in the airways, with neutrophils assembling in pulmonary capillaries, sputum and BALf [98].…”

Transforming growth factor-β type II receptor in pulmonary arteries of patients with very severe COPD

“…Previous studies have shown an increased number of inflammatory cells [8,9] in pulmonary arteries from patients with COPD. Inflammatory cells are a source of cytokines and growth factors that may contribute to the development of structural and functional abnormalities of the vessel wall [23].…”

“…Moreover, some of them would have been ventilated before lung transplantation. Since it is known that smoking and ventilation may induce structural changes in pulmonary arteries, this may have influenced the results [9,35,36]. TGF-b AND VERY SEVERE COPD B. BEGHE ET AL.…”

“…By contrast, at variance with primary hypertension, the medial layer of the arteries is normal or only mildly thickened [6]. These structural changes are often associated with functional impairment of the endothelium [7] and with an inflammatory process in the adventitial layer [8,9]. The mechanisms underlying the development of these structural abnormalities in pulmonary arteries are still unknown.…”