Chest
Translating Basic Research Into Clinical PracticeAngiogenesis in Chronic Lung Disease
Section snippets
Severe Angioproliferative PH
Elevated pulmonary artery pressures in patients with PH have been largely attributed to vasoconstriction. However, in the past 10 years there has been emerging evidence that exuberant angioproliferation is also an important contributor to vascular resistance. Tuder et al2first reported in 1994 that exuberant endothelial cell growth and elements of inflammation were present in PH-associated plexiform lesions. As evidence for a process of disordered angiogenesis, Tuder and coworkers2demonstrated
Airspace Enlargement/Emphysema
In contrast to many forms of PH that are characterized by increased angiogenesis, emphysema is remarkable for a relative paucity of blood vessels. COPD patients have a significantly reduced capillary length and length density.12VEGF receptor blockade in an experimental emphysema model of COPD13induced the loss of microvessels and was associated with alveolar septal cell apoptosis and airspace enlargement. This result suggests that a normal alveolar structure is not maintained without capillary
Asthma
Angiogenesis has only been appreciated in more recent years as an important contributor to airway remodeling in patients with bronchial asthma. Engorgement of dilated and remodeled vessels is a consistent feature in the airways of patients with fatal asthma.19Both adults20, 21and children22with mild-to-moderate asthma have an increased number of subepithelial bronchial vessels compared with nonasthmatic subjects, suggesting that angiogenesis is potentially a central component in the progression
Pulmonary Fibrosis
Although it has been acknowledged that some patients with interstitial lung disease have a pulmonary vascular disease component, usually characterized by the muscularization of small arteries, relatively little attention has been paid to the microvasculature. Cosgrove et al24examined lung tissue samples obtained from patients with interstitial lung disease. They examined histochemically the vascular density in the fibroblastic foci and found that the vessel density was decreased in association
Angiogenesis and Repair in Late-Phase Acute Lung Injury
The aftermath of acute lung injury (ALI)/ARDS is typically characterized by the resolution of inflammation by apoptosis and phagocytic clearance of dead cells, and epithelial and endothelial proliferation with the reestablishment of a functional gas-exchanging alveolar-capillary interface. Hyperactivation of the LSMP, however, may account for the progression to fibroproliferative ARDS with progressive intraalveolar and intraseptal angiofibroproliferation.28The result is chronic lung disease
Conclusions
Angiogenesis is a fundamental principle of vascular remodeling and repair. However, the association of pulmonary vascular cell apoptosis as an initiating mechanism for angiogenesis in chronic lung disorders has not been widely appreciated. This review has described in a broad fashion how disordered angiogenesis may be implicated in the disease pathogenesis of PH, emphysema, asthma, pulmonary fibrosis, and late-phase ARDS, and in regulation of the progression to chronic lung disease. An emerging
References (48)
- et al.
Loss of caveolin and heme oxygenase expression in severe pulmonary hypertension
Chest
(2006) - et al.
Muscle-targeted deletion of VEGF and exercise capacity in mice
Respir Physiol Neurobiol
(2006) Pulmonary pathology of the adult respiratory distress syndrome
Clin Chest Med
(1990)- et al.
Long-term assessment of lung function in survivors of severe ARDS
Chest
(2003) - et al.
Regulation of angiogenesis by hypoxia-inducible factor 1
Crit Rev Oncol Hematol
(2006) - et al.
Matrix metalloproteinases and matrix metalloproteinase inhibitors in acute lung injury
Hum Pathol
(2006) - et al.
VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization
FASEB J
(2006) - et al.
Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension
Am J Pathol
(1994) Pulmonary emphysema with special reference to vascular changes
Am Rev Respir Dis
(1959)- et al.
Vascular endothelial growth factor in the lung
Am J Physiol Lung Cell Mol Physiol
(2006)
The challenges of chronic obstructive pulmonary disease (COPD): a perspective
COPD
Emphysema: an autoimmune vascular disease?
Proc Am Thorac Soc
Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesis
J Pathol
Monoclonal endothelial cell proliferation is present in primary but not secondary pulmonary hypertension
J Clin Invest
Microsatellite instability of endothelial cell growth and apoptosis genes within plexiform lesions in primary pulmonary hypertension
Circ Res
Peroxisome proliferator-activated receptor γ (PPARγ) expression is decreased in pulmonary hypertension and affects endothelial cell growth
Circ Res
Lung morphometry by unbiased methods in emphysema: bronchial and blood vessel volume, alveolar surface area and capillary length
APMIS
Inhibition of VEGF receptors causes lung cell apoptosis and emphysema
J Clin Invest
Is alveolar destruction and emphysema in chronic obstructive pulmonary disease an immune disease?
Proc Am Thorac Soc
Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema
Am J Respir Crit Care Med
Correlation of lung surface area to apoptosis and proliferation in human emphysema
Eur Respir J
Lovastatin enhances clearance of apoptotic cells (efferocytosis) with implications for chronic obstructive pulmonary disease
J Immunol
Small airways dimensions in asthma and in chronic obstructive pulmonary disease
Am Rev Respir Dis
Increased vascularity of the bronchial mucosa in mild asthma
Am J Respir Crit Care Med
Cited by (68)
Soluble ECM promotes organotypic formation in lung alveolar model
2022, BiomaterialsCitation Excerpt :We then looked into another application of hFLO, a model for hypoxia-induced angiogenesis [65] which can mature to full perfusability [66]. Blood vessel formation is an important process which affects several lung diseases including cancer [67] and pulmonary hypertension [68]. Previous vascular organoid methods use of hypoxia (5% O2) and supplementation of proangiogenic factors vascular endothelial growth factor (VEGF) and fibroblasts growth factor 2 (FGF2) to induce vascular endothelial branching, differentiation and maturation [69].
Therapeutic targets in lung tissue remodelling and fibrosis
2021, Pharmacology and TherapeuticsGroup 3 PH: Clinical Features and Treatment
2021, Encyclopedia of Respiratory Medicine, Second EditionCdc42 regulates LPS-induced proliferation of primary pulmonary microvascular endothelial cells via ERK pathway
2017, Microvascular ResearchCitation Excerpt :Thus, the complete rehabilitation of PMVECs after injury mainly depends on cell proliferation around the lesions. However, some investigators have suggested that there is a pulmonary structure homeostasis, or balance, in which endothelial cells are continuously cycled through proliferation and apoptosis (Gargett and Rogers, 2001; Voelkel et al., 2007). Disruptions to this balance are thought to lead to chronic pulmonary or vascular disease.
A method for evaluating the murine pulmonary vasculature using micro-computed tomography
2017, Journal of Surgical ResearchCitation Excerpt :The lung is a complex organ that is composed of airways, blood vessels, and parenchyma. Acquired diseases such as emphysema and bronchopulmonary dysplasia, and congenital diseases such as congenital diaphragmatic hernia, congenital heart disease, and primary pulmonary hypertension may have alterations in the pulmonary vasculature from vessel wall remodeling and reduction in vessel numbers due to vessel rarefaction or failed angiogenesis.1-6 Pulmonary hypertension is a source of significant morbidity and mortality.
The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.