Angiogenesis in asthma: Altered angiogenic potential of bronchial smooth muscle cells of asthmatic patients

Aims: Airway remodeling, a key pathology in asthma, includes thickening of the airway wall, hypertrophy and hyperplasia of bronchial smooth muscle cells (BSMC), and increased vascularity. BSMC are known to produce angiogenic factors.

Objective: To compare angiogenic potential of BSMC from asthmatic and non-asthmatic patients and to identify asthma-specific angiogenic factors.

Methods: Primary BSMC were isolated from human airway tissue of asthmatic and non-asthmatic patients. Conditioned medium (CM) collected from BSMC isolates was tested for angiogenic capacity using the endothelial cell (EC)-spheroid in vitro angiogenesis assay. Proangiogenic factors in CM were quantified using a human angiogenesis antibody array and enzyme linked immunosorbent assay.

Results: Induction of sprout outgrowth from EC-spheroids by CM of BSMC from asthma patients was increased compared with CM of control BSMC (twofold, p<0.001). Levels of ENA-78, GRO-α and IL-8 were elevated in CM of BSMC from asthma patients (p<0.05 vs. non-asthmatic patients) Furthermore levels of VEGF, a potent inductor of angiogenesis, were analyzed and confirmed to be increased in CM from BSMC of asthmatics. SB 265610, a competitive antagonist of chemokine (CXC-motif) receptor 2 (CXCR2), attenuated the increased sprout outgrowth induced by CM of asthma patient-derived BSMC.

Conclusions: BSMC isolated from asthma patients exhibit increased angiogenic potential. CXCR2 ligands produced by BSMC may play a decisive role in directing the neovascularization in the sub-epithelial cell layers of the lung of asthma patients.

Implications: Counteracting neovascularization induced through CXCR2 may represent a novel strategy to reduce airway remodeling in asthma.

This study was supported by a research grant of the Swiss National Foundation (#320030_124905/1)