Dataset Information
Impaired neoangiogenesis in ??-adrenoceptor gene-deficient mice: restoration by intravascular human ??-adrenoceptor gene transfer and role of NF?B and CREB transcription factors.
Ontology highlight
ABSTRACT: Background and purpose
There is much evidence supporting the role of ??-adrenoceptors (??AR) in angiogenesis but the mechanisms underlying their effects have not been elucidated. Hence, we studied post-ischaemic angiogenesis in the hindlimb (HL) of ??AR knock-out mice (??AR-/-) in vivo and explored possible molecular mechanisms in vitro.Experimental approach
Femoral artery resection (FAR) was performed in wild-type and ??AR-/- mice and adaptive responses to chronic HL ischaemia were explored; blood flow was measured by ultrasound and perfusion of dyed beads, bone rarefaction, muscle fibrosis and skin thickness were evaluated by immunoflourescence and morphometric analysis. Intrafemoral delivery of an adenovirus encoding the human ??AR (AD??AR) was used to reinstate ??ARs in ??AR-/- mice. Molecular mechanisms were investigated in mouse-derived aortic endothelial cells (EC) in vitro, focusing on NF?B activation and transcriptional activity.Results
Angiogenesis was severely impaired in ??AR-/- mice subjected to FAR, but was restored by gene therapy with AD??AR. The proangiogenic responses to a variety of stimuli were impaired in ??AR-/- EC in vitro. Moreover, removal of ??ARs impaired the activation of NF?B, a transcription factor that promotes angiogenesis; neither isoprenaline (stimulates ?ARs) nor TNF? induced NF?B activation in ??AR(-/-) EC. Interestingly, cAMP response element binding protein (CREB), a transcription factor that counter regulates NF?B, was constitutively increased in ??AR(-/-) ECs. AD??AR administration restored ??AR membrane density, reduced CREB activity and reinstated the NF?B response to isoprenaline and TNF?.Conclusions and implications
Our results suggest that ??ARs control angiogenesis through the tight regulation of nuclear transcriptional activity.
SUBMITTER: Ciccarelli M
PROVIDER: S-EPMC3041259 | biostudies-literature | 2011 Feb
REPOSITORIES: biostudies-literature
Publications
Impaired neoangiogenesis in β₂-adrenoceptor gene-deficient mice: restoration by intravascular human β₂-adrenoceptor gene transfer and role of NFκB and CREB transcription factors.
British journal of pharmacology 20110201 3
<h4>Background and purpose</h4>There is much evidence supporting the role of β₂-adrenoceptors (β₂AR) in angiogenesis but the mechanisms underlying their effects have not been elucidated. Hence, we studied post-ischaemic angiogenesis in the hindlimb (HL) of β₂AR knock-out mice (β₂AR-/-) in vivo and explored possible molecular mechanisms in vitro.<h4>Experimental approach</h4>Femoral artery resection (FAR) was performed in wild-type and β₂AR-/- mice and adaptive responses to chronic HL ischaemia w ...[more]
