Role of angiogenesis and vascular remodeling in chronic obstructive pulmonary disease

Abstract

Recently, angiogenesis and pulmonary vascular remodeling in COPD has been investigated. It has been hypothesized that endothelial dysfunction might be an initiating event that promotes vessel remodeling in COPD. Inflammatory tissue--a pivotal pathological feature of COPD--often hypoxic, can induce angiogenesis through upregulation of factors such as VEGF or FGF and regulators of angiogenesis such as chemokines (CXC family), acting either as angiogenic or angiostatic. Angiopoietins are distinct molecules that act in association with VEGF at different stages of angiogenic process. The regulation of angiogenesis is determined by a dual, yet opposing balance of angiogenic and angiostatic factors that promote or inhibit neovascularization, respectively, not yet elucidated in detail in COPD. Recent studies suggested an increased expression of VEGF in pulmonary muscular arteries of patients with moderate COPD and also in smokers with normal lung function. This was also associated with enlargement of the arterial wall. However, in patients with severe emphysema, the expression of VEGF tended to be low, despite intense vascular remodelling. Furthermore, it has been suggested that VEGF might be involved in the pathogenesis of emphysema through apoptotic mechanisms. Experimental studies showed that the lung microvascular endothelial cells (including the alveolar septal capillary cells) are particularly vulnerable and dependent on VEGF for their survival. Apoptosis of endothelial, leading to the loss of capillaries may well be a central mechanism in patients with emphysema and muscle wasting. This review article summarizes the current knowledge regarding the contribution of vascular remodeling, as well as the pathogenetic and therapeutic implications of pivotal angiogenic mediators, in COPD.

Figure 1

Angiogenetic process in COPD. The angiogenetic pathway is stimulated when inflamed, hypoxic, or injured tissues produce and release different angiogenetic promoters. Loss of the pulmonary vascular bed has been suggested to lead to the formation of new vessels comprising lung tissue remodeling-like changes in mucosal tissue, fiber types and/or fibrosis, pulmonary and systemic inflammation, lung vascular remodeling, and angiogenesis.