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

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.

journal_name

Blood

journal_title

Blood

authors

Launay JM,Hervé P,Callebert J,Mallat Z,Collet C,Doly S,Belmer A,Diaz SL,Hatia S,Côté F,Humbert M,Maroteaux L

doi

10.1182/blood-2011-06-358374

subject

Has Abstract

pub_date

2012-02-16 00:00:00

pages

1772-80

issue

7

eissn

0006-4971

issn

1528-0020

pii

blood-2011-06-358374

journal_volume

119

pub_type

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