Budesonide/formoterol decreases expression of vascular endothelial growth factor (VEGF) and VEGF receptor 1 within airway remodelling in asthma.
BACKGROUND
Angiogenesis and microvascular remodelling may play a vital role in the chronic inflammatory process within asthma. One of the most important factors involved in angiogenesis is vascular endothelial growth factor (VEGF). In this study we hypothesised that an increased expression of VEGF may be involved in airway remodelling in asthma patients. To this end, we compared the histology and expression levels of VEGF and one of its receptors (VEGFR1) in bronchial tissues of patients with asthma compared with control patients. We also investigated the effect of treatment with budesonide/formoterol (Symbicort; AstraZeneca, Lund, Sweden) in the relationship between VEGF and airway remodelling.


METHODS
Bronchial tissues were obtained from patients attending the West China Hospital from April to November 2006. Thirteen patients were diagnosed with moderate asthma and 10 others were treated as control. Histological and immunohistochemical comparisons between asthmatic and control patients were made at baseline, and (for asthmatic subjects) following 6 months of treatment with budesonide/formoterol.


RESULTS
Compared with control patients, asthmatic patients had significantly decreased respiratory parameters, including forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV(1)) (% predictive). Furthermore, patients with asthma had submucosal gland hyperplasia, increased smooth muscle mass, increased subepithelial fibrosis and neovascularisation. Asthmatic patients also exhibited increased expression of VEGF and VEGFR1 within epithelial cells. The increased expression of VEGF and its receptor correlated well with airway remodelling, airflow obstruction and airway hyper-responsiveness. After treatment with budesonide/formoterol for 6 months, the expression of VEGF and VEGFR1 was decreased, with correlatory decreased airway remodelling in patients with asthma.


CONCLUSIONS
The increased expression of VEGF and VEGFR(1) in asthmatic patients is accompanied by an increased number and size of blood vessels in asthmatic airways, as well as airway remodelling. Budesonide/formoterol therapy for 6 months can decrease the expression of VEGF and VEGFR(1) alongside airway remodelling in asthma. The inhibition of VEGF and its receptor may be a good therapeutic strategy for asthma.
Wang
Ke
K
Department of Respiratory Medicine, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. wang2ke@yahoo.com.cn
Liu
Chun-Tao
CT
Wu
Yong-Hong
YH
Feng
Yu-Ling
YL
Bai
Hong-Li
HL
D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019819:Budesonide / Q000494:pharmacology / Q000627:therapeutic use*; D000069502:Budesonide, Formoterol Fumarate Drug Combination; D004338:Drug Combinations; D004983:Ethanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D012129:Respiratory Function Tests; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis*
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000069502:Budesonide, Formoterol Fumarate Drug Combination; D004338:Drug Combinations; D004983:Ethanolamines; D042461:Vascular Endothelial Growth Factor A; D019819:Budesonide; D040281:Vascular Endothelial Growth Factor Receptor-1