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Published ahead of print on April 27, 2006, doi:10.1164/rccm.200510-1558OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 2, July 2006, 161-170

A more recent version of this article appeared on July 15, 2006
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Submitted on October 4, 2005
Accepted on April 26, 2006

Vascular Endothelial Growth Factor Modulates Matrix Metalloproteinase-9 Expression in Asthma

Kyung Sun Lee1, Kyung Hoon Min1, So Ri Kim1, Seoung Ju Park1, Hee Sun Park1, Gong Yong Jin1, and Yong Chul Lee1*

1 Department of Internal Medicine, Department of Radiology, Airway Remodeling Laboratory and Research Center for Allergic Immune Diseases, Chonbuk National University Medical School, Jeonju, Korea, Republic of

* To whom correspondence should be addressed. E-mail: leeyc{at}chonbuk.ac.kr.

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 asthma patients 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 pathophysiological 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 pathophysiological 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.
Key words: airway inflammation, extracellular matrix, permeability, remodeling




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