Key result
GS-6201 treatment or genetic removal of the A2B receptor attenuated vascular remodeling and pulmonary hypertension in mice exposed to bleomycin.
Why the study?
Does A2BR antagonism or genetic deletion reduce vascular remodeling and pulmonary hypertension in a mouse model of bleomycin-induced pulmonary fibrosis?
Does A2BR antagonism or genetic deletion reduce vascular remodeling and pulmonary hypertension in a mouse model of bleomycin-induced pulmonary fibrosis?
Answers are grounded in this paper and cite their sources.
Pharmacological blockade or genetic deletion of the A2B adenosine receptor attenuates vascular remodeling and pulmonary hypertension in a mouse model of interstitial lung disease, identifying a potential novel therapeutic target.
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
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Karmouty‐Quintana et al. (2012) studied Pulmonary hypertension associated with interstitial lung disease. GS-6201 or genetic removal of A2B receptor was evaluated on Vascular remodeling and pulmonary hypertension. GS-6201 treatment or genetic removal of the A2B receptor attenuated vascular remodeling and pulmonary hypertension in mice exposed to bleomycin.
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