Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertension

Launay, Jean-Marie, Herve, Phillipe, Callebert, Jacques, Mallat, Ziad, Collet, Corinne, Doly, Stephane, Belmer, Arnauld, Diaz, Silvina L., Hatia, Sarah, Cote, Francine, Humbert, Marc, & Maroteaux, Luc (2012) Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertension. Blood, 119(7), pp. 1772-1780.

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Abstract

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by lung endothelial dysfunction and vascular remodeling. Recently, bone marrow progenitor cells have been localized to PAH lungs, raising the question of their role in disease progression. Independently, serotonin (5-HT) and its receptors have been identified as contributors to the PAH pathogenesis. We hypothesized that 1 of these receptors, 5-HT(2B), is involved in bone marrow stem cell mobilization that participates in the development of PAH and pulmonary vascular remodeling. A first study revealed expression of 5-HT(2B) receptors by circulating c-kit(+) precursor cells, whereas mice lacking 5-HT(2B) receptors showed alterations in platelets and monocyte-macrophage numbers, and in myeloid lineages of bone marrow. Strikingly, mice with restricted expression of 5-HT(2B) receptors in bone marrow cells developed hypoxia or monocrotaline-induced increase in pulmonary pressure and vascular remodeling, whereas restricted elimination of 5-HT(2B) receptors on bone marrow cells confers a complete resistance. Moreover, ex vivo culture of human CD34(+) or mice c-kit(+) progenitor cells in the presence of a 5-HT(2B) receptor antagonist resulted in altered myeloid differentiation potential. Thus, we demonstrate that activation of 5-HT(2B) receptors on bone marrow lineage progenitors is critical for the development of PAH.

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ID Code: 75296
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Additional URLs:
Keywords: 5-HT2B, Bone marrow, pulmonary hypertension
DOI: 10.1182/blood-2011-06-358374
ISSN: 1528-0020
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > CARDIOVASCULAR MEDICINE AND HAEMATOLOGY (110200) > Cardiology (incl. Cardiovascular Diseases) (110201)
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 19 Aug 2014 22:26
Last Modified: 27 Jan 2015 06:43

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