Chest
Translating Basic Research Into Clinical PracticePulmonary Vascular Involvement in COPD
Section snippets
Pulmonary Vascular Remodeling in COPD
Remodeling is a process that causes thickening of the arterial wall and is thought to increase resistance by causing the vessel wall to encroach into the lumen and reduce its diameter. In COPD patients, pulmonary vascular remodeling affects small and precapillary arteries, and has been identified at different degrees of disease severity. Intimal enlargement is the most prominent feature of pulmonary vascular remodeling. It is apparent in arteries of different sizes, although it is more
Inflammatory Changes
COPD is an inflammatory disease, hence, inflammatory cells might contribute to the alterations of pulmonary vessels. Indeed, the extent of pulmonary vascular remodeling correlates with the severity of inflammatory cell infiltrate in small airways.2, 11 Patients with COPD have an increased number of inflammatory cells infiltrating the adventitia of pulmonary muscular arteries, compared with nonsmokers.12 This inflammatory infiltrate is largely constituted by activated T lymphocytes with a
Endothelial Dysfunction
Endothelial cells play a crucial role in the regulation of vascular homeostasis.14 In pulmonary vessels, endothelial cells contribute to the reduced vascular tone,15 regulate vessel adaptation to increased flow,16 and modulate hypoxic vasoconstriction.17, 18 Endothelial dysfunction of the pulmonary arteries has been shown with different degrees of COPD severity, as follows: patients with end-stage COPD who had undergone lung transplantation19; and patients with mild-to-moderate COPD.3 The
Stem Cells and Vascular Remodeling in COPD
The idea of a maintenance program in the adult lung has emerged in the past few years.25 The lung copes with external challenges by inhaled particles, toxic gases, and invading microorganisms. The defense against this external injury depends on immune mechanisms and an efficient system for removing and replacing apoptotic cells. Stem cells may play a critical role in lung homeostasis since they retain their ability to replicate and differentiate into structural cells. Both resident and bone
Pathobiology of Pulmonary Vascular Changes in COPD
Hypoxia has been classically considered to be the major pathogenic mechanism of pulmonary hypertension in COPD. However, its role is currently being reconsidered because pulmonary vascular remodeling and endothelial dysfunction can be observed in patients with mild COPD who do not have hypoxemia and in smokers with normal lung function,2, 4, 12 and because long-term oxygen therapy does not reverse pulmonary hypertension.31
Observations1 point out that cigarette smoke products might be at the
Clinical Implications
The results of basic research into the vascular biology of the pulmonary circulation in COPD patients have identified the following several issues having potential clinical relevance: (1) structural and functional changes in pulmonary vessels are highly prevalent in all disease stages; (2) in patients with mild-to-moderate disease, these changes may not cause pulmonary hypertension at rest but might produce it during exercise and, eventually, may contribute to exercise limitation; (3) the
Endothelium-Targeted Treatment
The treatment options for COPD-associated pulmonary vascular abnormalities are limited. To date, long-term oxygen therapy for the treatment of hypoxemia is the only treatment that has demonstrated efficacy in slowing down or reversing the progression of pulmonary hypertension.31 Nevertheless, pulmonary arterial pressure rarely returns to normal values, and the structural abnormalities of pulmonary vessels remain unaltered.9 Treatment with conventional vasodilators, such as calcium channel
Conclusions
Structural and functional impairment of pulmonary vessels are early phenomena in the natural history of COPD. Cigarette smoke products are now identified as the most likely causative agents of the initial changes in pulmonary circulation through either a direct effect on endothelial cells or an inflammatory mechanism. The combination of endothelial dysfunction, vessel remodeling and inflammatory cell infiltrate conform the basis for the development of pulmonary hypertension in COPD. Treatment
References (47)
- et al.
Worsening of pulmonary gas exchange with nitric oxide inhalation in chronic obstructive pulmonary disease
Lancet
(1996) - et al.
Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell
Cell
(2001) Circulating vascular progenitor cells contribute to vascular repair, remodeling, and lesion formation
Trends Cardiovasc Med
(2003)- et al.
Cigarette smoke induces rapid changes in gene expression in pulmonary arteries
Lab Invest
(2002) - et al.
Pulmonary hypertension in chronic obstructive pulmonary disease
Eur Respir J
(2003) - et al.
Pulmonary vascular abnormalities and ventilation-perfusion relationships in mild chronic obstructive pulmonary disease
Am J Respir Crit Care Med
(1994) - et al.
Endothelial dysfunction in pulmonary arteries of patients with mild COPD
Am J Physiol Lung Cell Mol Physiol
(1998) - et al.
Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD
Eur Respir J
(2002) - et al.
Pulmonary vascular structure and function in chronic obstructive pulmonary disease
Thorax
(1988) Regulation of differentiation of vascular smooth muscle cells
Physiol Rev
(1995)
Differentiation of smooth muscle cells in human blood vessels as defined by smoothelin, a novel marker for the contractile phenotype
Arterioscler Thromb Vasc Biol
Vimentin-containing smooth muscle cells in aortic intimal thickening after endothelial injury
Lab Invest
A pathophysiological study of 10 cases of hypoxic cor pulmonale
Q J Med
Analysis of the structure of the muscular pulmonary arteries in patients with pulmonary hypertension and COPD: National Institutes of Health Nocturnal Oxygen Therapy Trial
Lung
Lung disease in long-term cigarette smokers with and without chronic air-flow obstruction
Am Rev Respir Dis
Inflammatory reaction in pulmonary muscular arteries of patients with mild chronic obstructive pulmonary disease
Am J Respir Crit Care Med
CD8+ve cells in the lungs of smokers with chronic obstructive pulmonary disease
Am J Respir Crit Care Med
The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine
Nature
Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans
Circulation
Effect of inhibitors of nitric oxide release and action on vascular tone in isolated lungs of pig, sheep, dog and man
J Physiol
Endothelium-dependent and -independent responses to severe hypoxia in rat pulmonary artery
Am J Physiol
Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive lung disease
N Engl J Med
Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension
N Engl J Med
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