Sökning: onr:"swepub:oai:DiVA.org:uu-261311" >
Perlecan heparan su...
-
Chang, Ya-TingKarolinska Institutet
(författare)
Perlecan heparan sulfate deficiency impairs pulmonary vascular development and attenuates hypoxic pulmonary hypertension
- Artikel/kapitelEngelska2015
Förlag, utgivningsår, omfång ...
-
2015-05-06
-
Oxford University Press (OUP),2015
-
printrdacarrier
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:uu-261311
-
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-261311URI
-
https://doi.org/10.1093/cvr/cvv143DOI
-
https://lup.lub.lu.se/record/5456676URI
-
http://kipublications.ki.se/Default.aspx?queryparsed=id:131730130URI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
Aims Excessive vascular cell proliferation is an important component of pulmonary hypertension (PH). Perlecan is the major heparan sulfate (HS) proteoglycan in the vascular extracellular matrix. It binds growth factors, including FGF2, and either restricts or promotes cell proliferation. In this study, we have explored the effects of perlecan HS deficiency on pulmonary vascular development and in hypoxia-induced PH. Methods and results In normoxia, Hspg2(Delta 3/Delta 3) mice, deficient in perlecan HS, had reduced pericytes and muscularization of intra-acinar vessels. Pulmonary angiography revealed a peripheral perfusion defect. Despite these abnormalities, right ventricular systolic pressure (RVSP) and myocardial mass remained normal. After 4 weeks of hypoxia, increases in the proportion of muscularized vessels, RVSP, and right ventricular hypertrophy were significantly less in Hspg2(Delta 3/Delta 3) compared with wild type. The early phase of hypoxia induced a significantly lower increase in fibroblast growth factor receptor-1 (FGFR1) protein level and receptor phosphorylation, and reduced pulmonary artery smooth muscle cell (PASMC) proliferation in Hspg2(Delta 3/Delta 3). At 4 weeks, FGF2 mRNA and protein were also significantly reduced in Hspg2(Delta 3/Delta 3) lungs. Ligand and carbohydrate engagement assay showed that perlecan HS is required for HS-FGF2-FGFR1 ternary complex formation. In vitro, proliferation assays showed that PASMC proliferation is reduced by selective FGFR1 inhibition. PASMC adhesion to fibronectin was higher in Hspg2(Delta 3/Delta 3) compared with wild type. Conclusions Perlecan HS chains are important for normal vascular arborization and recruitment of pericytes to pulmonary vessels. Perlecan HS deficiency also attenuates hypoxia-induced PH, where the underlying mechanisms involve impaired FGF2/FGFR1 interaction, inhibition of PASMC growth, and altered cell-matrix interactions.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Tseng, Chi-Nan
(författare)
-
Tannenberg, PhilipKarolinska Institutet
(författare)
-
Eriksson, LinneaKarolinska Institutet
(författare)
-
Yuan, Ke
(författare)
-
Perez, Vinicio A. de Jesus
(författare)
-
Lundberg, JohanKarolinska Institutet
(författare)
-
Lengquist, MarietteKarolinska Institutet
(författare)
-
Botusan, Ileana RuxandraKarolinska Institutet
(författare)
-
Catrina, Sergiu-BogdanKarolinska Institutet
(författare)
-
Tran, Phan-KietKarolinska Institutet,Lund University,Lunds universitet,Uppsala universitet,Institutionen för kirurgiska vetenskaper,Kärlväggsbiologi,Forskargrupper vid Lunds universitet,Vessel Wall Biology,Lund University Research Groups(Swepub:lu)med-pat
(författare)
-
Hedin, UlfKarolinska Institutet
(författare)
-
Tran Lundmark, KarinKarolinska Institutet,Lund University,Lunds universitet,Kärlväggsbiologi,Forskargrupper vid Lunds universitet,Vessel Wall Biology,Lund University Research Groups(Swepub:lu)med-kt_
(författare)
-
Karolinska InstitutetInstitutionen för kirurgiska vetenskaper
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Cardiovascular Research: Oxford University Press (OUP)107:1, s. 20-310008-63631755-3245
Internetlänk
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Chang, Ya-Ting
-
Tseng, Chi-Nan
-
Tannenberg, Phil ...
-
Eriksson, Linnea
-
Yuan, Ke
-
Perez, Vinicio A ...
-
visa fler...
-
Lundberg, Johan
-
Lengquist, Marie ...
-
Botusan, Ileana ...
-
Catrina, Sergiu- ...
-
Tran, Phan-Kiet
-
Hedin, Ulf
-
Tran Lundmark, K ...
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Kardiologi
- Artiklar i publikationen
-
Cardiovascular R ...
- Av lärosätet
-
Uppsala universitet
-
Lunds universitet
-
Karolinska Institutet