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Hematopoietic stem cell transplantation alters susceptibility to pulmonary hypertension in Bmpr2-deficient mice.

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cam.issuedOnline2018-08-30
dc.contributor.authorCrosby, Alexi
dc.contributor.authorToshner, Mark R
dc.contributor.authorSouthwood, Mark R
dc.contributor.authorSoon, Elaine
dc.contributor.authorDunmore, Benjamin J
dc.contributor.authorGroves, Emily
dc.contributor.authorMoore, Stephen
dc.contributor.authorWright, Penny
dc.contributor.authorOttersbach, Katrin
dc.contributor.authorBennett, Cavan
dc.contributor.authorGuerrero, Jose
dc.contributor.authorGhevaert, Cedric
dc.contributor.authorMorrell, Nicholas W
dc.contributor.orcidToshner, Mark [0000-0002-3969-6143]
dc.contributor.orcidSoon, Elaine [0000-0002-5744-5014]
dc.contributor.orcidGhevaert, Cedric [0000-0002-9251-0934]
dc.contributor.orcidMorrell, Nicholas [0000-0001-5700-9792]
dc.date.accessioned2018-11-16T00:31:10Z
dc.date.available2018-11-16T00:31:10Z
dc.date.issued2018
dc.description.abstractIncreasing evidence suggests that patients with pulmonary arterial hypertension (PAH) demonstrate abnormalities in the bone marrow (BM) and hematopoietic progenitor cells. In addition, PAH is associated with myeloproliferative diseases. We have previously demonstrated that low-dose lipopolysaccharide (LPS) is a potent stimulus for the development of PAH in the context of a genetic PAH mouse model of BMPR2 dysfunction. We hypothesized that the hematopoietic progenitor cells might be driving disease in this model. To test this hypothesis, we performed adoptive transfer of BM between wild-type (Ctrl) and heterozygous Bmpr2 null (Mut) mice. Sixteen weeks after BM reconstitution, mice were exposed to low-dose chronic LPS (0.5 mg/kg three times a week for six weeks). Mice underwent right heart catheterization and tissues were removed for histology. After chronic LPS dosing, Ctrl mice in receipt of Mut BM developed PAH, whereas Mut mice receiving Ctrl BM were protected from PAH. BM histology demonstrated an increase in megakaryocytes and there was an increase in circulating platelets in Ctrl mice receiving Mut BM. These findings demonstrate that the hematopoietic stem cell compartment is involved in the susceptibility to PAH in the Mut mouse. The results raise the possibility that hematopoietic stem cell transplantation might be a potential treatment strategy in genetic forms of PAH.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.32516
dc.identifier.eissn2045-8940
dc.identifier.issn2045-8932
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285145
dc.languageeng
dc.language.isoeng
dc.publisherWiley
dc.publisher.urlhttp://dx.doi.org/10.1177/2045894018801642
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectLPS
dc.subjectbone marrow
dc.subjectmegakaryocytes
dc.titleHematopoietic stem cell transplantation alters susceptibility to pulmonary hypertension in Bmpr2-deficient mice.
dc.typeArticle
dcterms.dateAccepted2018-08-30
prism.issueIdentifier4
prism.publicationDate2018
prism.publicationNamePulm Circ
prism.startingPage2045894018801642
prism.volume8
pubs.funder-project-idNHS Blood and Transplant (NHSBT)
pubs.funder-project-idMedical Research Council (G0802261)
pubs.funder-project-idMedical Research Council (MC_PC_12009)
pubs.funder-project-idMedical Research Council (MR/L022982/1)
pubs.funder-project-idMedical Research Council (MR/P007813/1)
pubs.funder-project-idMedical Research Council (MR/R008051/1)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idMedical Research Council (MC_UU_12012/5)
pubs.funder-project-idMedical Research Council (MC_PC_12012)
pubs.funder-project-idMedical Research Council (G0802261/1)
rioxxterms.licenseref.startdate2018-10
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1177/2045894018801642

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