Angiogenesis and Vascular Remodeling in Chronic Airway Diseases

Abstract

Asthma and chronic obstructive pulmonary disease remain a global health problem, with increasing morbidity and mortality. Despite differences in the causal agents, both diseases exhibit various degrees of inflammatory changes, structural alterations of the airways leading to airflow limitation. The existence of transient disease phenotypes which overlap both diseases and which progressively decline the lung function has complicated the search for an effective therapy. Important characteristics of chronic airway diseases include airway and vascular remodeling, of which the molecular mechanisms are complex and poorly understood. Recently, we and others have shown that airway smooth muscle (ASM) cells are not only structural and contractile components of airways, rather they bear capabilities of producing large number of pro-inflammatory and mitogenic factors. Increase in size and number of blood vessels both inside and outside the smooth muscle layer as well as hyperemia of bronchial vasculature are contributing factors in airway wall remodeling in patients with chronic airway diseases, proposing for the ongoing mechanisms like angiogenesis and vascular dilatation. We believe that vascular changes directly add to the airway narrowing and hyper-responsiveness by exudation and transudation of proinflammatory mediators, cytokines and growth factors; facilitating trafficking of inflammatory cells; causing oedema of the airway wall and promoting ASM accumulation. One of the key regulators of angiogenesis, vascular endothelial growth factor in concerted action with other endothelial mitogens play pivotal role in regulating bronchial angiogenesis. In this review article we address recent advances in pulmonary angiogenesis and remodelling that contribute in the pathogenesis of chronic airway diseases.

Pulmonary vascular changes in asthma and COPD

“…Thereafter, a number of studies reported the involvement of specific growth factors, such as fibroblast growth factor (FGF), transforming growth factor (TGF) β1 and vascular endothelial growth factor (VEGF), during vascular remodelling in asthma and COPD [9][10][11][12]. Vascular remodelling, including thickening of the intimal and medial layers due to vascular smooth muscle (VSM) cell hypertrophy, is reported to progressively decline lung function [10,13] and vascular alterations in the pulmonary circulation may impair gas exchange in the alveolar compartments that result in pulmonary hypertension in some COPD patients [14].…”

Bronchial asthma, wheezing, flatter: probable relationships

“…В соответствии с со временными представлениями БА -это хроничес кое персистирующее воспалительное заболевание, ведущее к структурным изменениям и ремоделиро ванию дыхательных путей (ДП). В понятие «ремо делирование» включены следующие основные ком поненты: гипертрофия гладких мышц, гиперплазия бокаловидных клеток, субэпителиальный (субба зальный) фиброз и ангиогенез [1][2][3][4][5]; развитие брон хиальной гиперреактивности [6].…”

“…В последние годы накапливается все больше данных об изменениях микроциркуляторного русла и ремоде лирование сосудов ДП у больных БА и ХОБЛ [46][47][48][49].…”

“…В соответствии с со временными представлениями БА -это хроничес кое персистирующее воспалительное заболевание, ведущее к структурным изменениям и ремоделиро ванию дыхательных путей (ДП). В понятие «ремо делирование» включены следующие основные ком поненты: гипертрофия гладких мышц, гиперплазия бокаловидных клеток, субэпителиальный (субба зальный) фиброз и ангиогенез [1][2][3][4][5]; развитие брон хиальной гиперреактивности [6].Хронический воспалительный процесс, ремоде лирование ДП, бронхиальная гиперреактивность, бронхиальная обструкция определяют характерные клинические симптомы БА -свистящие хрипы, ка шель, диспноэ [7][8][9], причем свистящее дыхание относится к наиболее частым из них. Так, по данным эпидемиологического исследования ECRHS (Euro pean Community Respiratory Health Survey) о распрост раненности симптомов БА среди лиц (мужчин и жен щин) 20-44 летнего возраста приступы удушья встречаются в среднем у 9,7 %, а свистящее дыха ние -у 32,0 % больных [10].…”

IL-25 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma model

“…Nowadays, it is well accepted that in addition to inflammation, airways remodelling is also a hallmark feature of asthma which has been implicated in regulating disease severity and control [2][3][4]. Airways remodelling refers to structural changes including loss of epithelial integrity, thickening of the subepithelial basement membrane caused by fibrosis, goblet cell metaplasia and submucosal gland enlargement, increased airway smooth muscle mass, increased airways vascularity and vascular remodelling [2][3][4]. Although the notion that airways remodelling is one of the key features of asthma is well established, the underlying mechanisms have not been fully clarified.…”