Local micro environmental factors are crucial in determining both susceptibility to vascular remodeling and the extent of angiogenesis. Major exogenous triggers of airway inflammation in asthma include viruses and inhaled aeroallergens, both of which are known to be associated with the production of angiogenic factors . These stimuli elicit reciprocal immune responses, through elaboration of Th1 and Th2 cytokines.
While there may be a genetic predisposition to asthmatic bronchial hyper reactivity, the link to exaggerated Th2 responses characteristic of atopic dermatitis asthma is currently less well defined. A link between airway inflammation and vessel remodeling may be understood by examining nonvascular actions of VEGF. Vascular endothelial growth factor levels are associated with increased severity of clinical asthma, and may enhance Th2 lung inflammation murine asthma models.
Together with the finding of VEGF production by mast cells, it is clear that there is a role in addition to its action on vessels in the effector arm of the early and late asthmatic responses.
Regulation of the inflammatory response in asthma occurs through intermediary transcription factors such as NF-xB, that also signal gene transcription for angiogenic factors including IL-8, ENA-78, and GRO-a. Indeed, endothelial cell cytokine production of angiogenic factors such as IL-8 is mediated by NF-xB. Treatment of asthma with inhaled corticosteroids may suppress NF-xB, and, coincidentally, local inflammation with angiogenesis bronchial asthma symptoms.
Cell infiltration, angiogenesis, and vessel leakage may also occur through the activation of structural cells, including fibroblasts, by viral infection that induces production of IL-8 and ENA-78. Nasal obstruction during viral upper respiratory tract infections indicates the significance of this mechanism to cause luminal occlusion, independent of atopic status.
With the stimuli of either infection or atopic inflammation, increased vascular surface area and endothelial fenestrations lead to increased plasma protein leakage. As well as elevated baseline leakage, remodeled bronchial asthma symptoms vessels in the submucosa are abnormally sensitive to substance P, but not to platelet-activating factor or serotonin, implying that at least infection is associated with a selective up regulation of NK1 receptors on the vasculature.
Inflammation and angiogenesis are codependent phenomena. The preparation of vessels with up regulated adhesion glycoprotein expression in an appropriate field, allows angiogenesis to arise from resident tissue progenitors, or alternatively from migrating angioblasts with endothelial lineage capacity.
