The vascular bed in COPD: pulmonary hypertension and pulmonary vascular alterations

Abstract

The loss of pulmonary vessels has been shown to be related to the severity of pulmonary hypertension in patients with chronic obstructive pulmonary disease (COPD). The severity of hypoxaemia is also related to pulmonary hypertension and pulmonary vascular resistance in these patients, suggesting that the hypoxic condition probably plays an important role in this form of pulmonary hypertension. However, pulmonary hypertension also develops in patients with mild COPD without hypoxaemia. Oxygen supplementation therapy often fails to reverse the pulmonary hypertension in these COPD patients, thus suggesting that the pulmonary vascular alterations in those patients may involve different sites of the pulmonary vasculature or a different form of vascular remodelling. It has recently been demonstrated that pulmonary vascular remodelling, resulting in pulmonary hypertension in COPD patients, can develop independently from parenchymal destruction and loss of lung vessels. We wonder whether the changes in the lung microenvironment due to hypoxia and vessel loss have a causative role in the development of pulmonary hypertension in patients with COPD. Herein we review the pathobiological features of the pulmonary vasculature in COPD patients and suggest that pulmonary hypertension can occur with and without emphysematous lung tissue destruction and with and without loss of lung vessels.

Figure 1.

A hypothetical mechanism underlying the pulmonary vascular remodelling in highlanders, chronic obstructive pulmonary disease (COPD) patients and idiopathic pulmonary arterial hypertension (IPAH) patients. In healthy highlanders, long-term alveolar hypoxia can cause pulmonary vascular alterations, including medial wall thickening and muscularisation of nonmuscularised arterioles with proliferative smooth muscle-like cells (SMLCs). These are caused by the high fluid shear stress owing to hypoxic pulmonary vasoconstriction (HPV), resulting in an elevated pulmonary arterial pressure. In the patients with COPD, both vascular injuries caused by toxic agents and airborne particulates, including tobacco smoke, and the haemodynamic changes induced by the hypoxic condition resulting from the parenchymal destruction and the decreased vascular bed, may have a role in inducing the neointimal lesions consisting of proliferative SMLCs in the pulmonary muscular arteries. These lesions are different from the pulmonary vascular alterations seen in highlanders and in the pulmonary hypertension models induced by chronic hypoxic exposure alone. In the patients with IPAH, the defining pulmonary vascular alterations are complex vascular lesions consisting of phenotypically altered and proliferating endothelial-like cells (ELCs). The distinction between the pathological features in IPAH and COPD seems to largely be the presence or absence of complex vascular lesions with phenotypically altered and proliferating ELCs. EC: endothelial cell; SMC: smooth muscle cell.