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Publication : Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension.

First Author  Launay JM Year  2002
Journal  Nat Med Volume  8
Issue  10 Pages  1129-35
PubMed ID  12244304 Mgi Jnum  J:79276
Mgi Id  MGI:2387725 Doi  10.1038/nm764
Citation  Launay JM, et al. (2002) Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension. Nat Med 8(10):1129-35
abstractText  Primary pulmonary hypertension is a progressive and often fatal disorder in humans that results from an increase in pulmonary blood pressure associated with abnormal vascular proliferation. Dexfenfluramine increases the risk of pulmonary hypertension in humans, and its active metabolite is a selective serotonin 5-hydroxytryptamine 2B (5-HT<inf>2B</inf>) receptor agonist. Thus, we investigated the contribution of the 5-HT<inf>2B</inf> receptor to the pathogenesis of pulmonary hypertension. Using the chronic-hypoxic-mouse model of pulmonary hypertension, we found that the hypoxia-dependent increase in pulmonary blood pressure and lung remodeling are associated with an increase in vascular proliferation, elastase activity and transforming growth factor-beta levels, and that these parameters are potentiated by dexfenfluramine treatment. In contrast, hypoxic mice with genetically or pharmacologically inactive 5-HT<inf>2B</inf> receptors manifested no change in any of these parameters. In both humans and mice, pulmonary hypertension is associated with a substantial increase in 5-HT<inf>2B</inf> receptor expression in pulmonary arteries. These data show that activation of 5-HT<inf>2B</inf> receptors is a limiting step in the development of pulmonary hypertension.
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