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The A 2B adenosine receptor modulates pulmonary hypertension associated with interstitial lung disease
Author(s) -
KarmoutyQuintana Harry,
Zhong Hongyan,
Acero Luis,
Weng Tingting,
Melicoff Ernestina,
West James D.,
Hemnes Anna,
Grenz Almut,
Eltzschig Holger K.,
Blackwell Timothy S.,
Xia Yang,
Johnston Richard A.,
Zeng Dewan,
Belardinelli Luiz,
Blackburn Michael R.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-200907
Subject(s) - pulmonary hypertension , medicine , interstitial lung disease , lung , idiopathic pulmonary fibrosis , bleomycin , endothelin receptor , endothelin receptor antagonist , pulmonary fibrosis , endothelin 1 , cardiology , pharmacology , endocrinology , receptor , chemotherapy
Development of pulmonary hypertension is a common and deadly complication of interstitial lung disease. Little is known regarding the cellular and molecular mechanisms that lead to pulmonary hypertension in patients with interstitial lung disease, and effective treatment options are lacking. The purpose of this study was to examine the adenosine 2B receptor (A 2B R) as a regulator of vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. To accomplish this, cellular and molecular changes in vascular remodeling were monitored in mice exposed to bleomycin in conjunction with genetic removal of the A 2B R or treatment with the A 2B R antagonist GS‐6201. Results demonstrated that GS‐6201 treatment or genetic removal of the A 2B R attenuated vascular remodeling and hypertension in our model. Furthermore, direct A 2B R activation on vascular cells promoted interleukin‐6 and endothelin‐1 release. These studies identify a novel mechanism of disease progression to pulmonary hypertension and support the development of A 2B R antagonists for the treatment of pulmonary hypertension secondary to interstitial lung disease.—Karmouty‐Quintana, H., Zhong, H., Acero, L., Weng, T., Melicoff, E., West, J. D., Hemnes, A., Grenz, A., Eltzschig, H. K., Blackwell, T. S., Xia, Y., Johnston, R. A., Zeng, D., Belardinelli, L., Blackburn, M. R. The A 2B adenosine receptor modulates pulmonary hypertension associated with interstitial lung disease. FASEB J. 26, 2546–2557 (2012). www.fasebj.org