RATIONALE: Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are mediators of airway inflammation and remodeling in asthma. OBJECTIVES: This study investigates a potential relationship between VEGF and MMP-9, and the mechanisms by which VEGF signaling regulates MMP-9 expression in asthma. METHODS: We evaluated whether levels of VEGF correlated with levels of MMP-9 in the sputum of asthma patients, and the effect of VEGF receptor inhibitors on MMP-9 expression in murine model of asthma. MEASUREMENTS AND MAIN RESULTS: We have found that levels of VEGF and MMP-9 are significantly higher in the sputum of patients with asthma than in healthy control subjects, and a significant correlation is found between the levels of VEGF and MMP-9. This study with the ovalbumin-induced model of asthma revealed the following typical pathophysiologic features of asthma in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased vascular permeability, and increased levels of MMP-9 and VEGF. Administration of VEGF receptor inhibitors reduced the pathophysiologic signs of asthma and decreased the increased expression of MMP-9 after ovalbumin inhalation. CONCLUSIONS: These results indicate that there is a close relationship between VEGF and MMP-9 expression and that inhibition of VEGF receptor down-regulates the expression of MMP-9. These findings suggest that VEGF signaling regulates MMP-9 expression and plays a critical role in initiation and maintenance of asthma.
RATIONALE: Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are mediators of airway inflammation and remodeling in asthma. OBJECTIVES: This study investigates a potential relationship between VEGF and MMP-9, and the mechanisms by which VEGF signaling regulates MMP-9 expression in asthma. METHODS: We evaluated whether levels of VEGF correlated with levels of MMP-9 in the sputum of asthmapatients, and the effect of VEGF receptor inhibitors on MMP-9 expression in murine model of asthma. MEASUREMENTS AND MAIN RESULTS: We have found that levels of VEGF and MMP-9 are significantly higher in the sputum of patients with asthma than in healthy control subjects, and a significant correlation is found between the levels of VEGF and MMP-9. This study with the ovalbumin-induced model of asthma revealed the following typical pathophysiologic features of asthma in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased vascular permeability, and increased levels of MMP-9 and VEGF. Administration of VEGF receptor inhibitors reduced the pathophysiologic signs of asthma and decreased the increased expression of MMP-9 after ovalbumin inhalation. CONCLUSIONS: These results indicate that there is a close relationship between VEGF and MMP-9 expression and that inhibition of VEGF receptor down-regulates the expression of MMP-9. These findings suggest that VEGF signaling regulates MMP-9 expression and plays a critical role in initiation and maintenance of asthma.
Authors: Hyun Lee; So Ri Kim; Youngman Oh; Seong Ho Cho; Robert P Schleimer; Yong Chul Lee Journal: Am J Respir Cell Mol Biol Date: 2014-04 Impact factor: 6.914
Authors: P F T Cezar-de-Mello; A M Vieira; V Nascimento-Silva; C G Villela; C Barja-Fidalgo; I M Fierro Journal: Br J Pharmacol Date: 2008-01-14 Impact factor: 8.739