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https://hdl.handle.net/2440/105139
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dc.contributor.author | Prosser, H. | - |
dc.contributor.author | Tan, J. | - |
dc.contributor.author | Dunn, L. | - |
dc.contributor.author | Patel, S. | - |
dc.contributor.author | Vanags, L. | - |
dc.contributor.author | Bao, S. | - |
dc.contributor.author | Ng, M. | - |
dc.contributor.author | Bursill, C. | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | Cardiovascular Research, 2014; 101(1):145-154 | - |
dc.identifier.issn | 0008-6363 | - |
dc.identifier.issn | 1755-3245 | - |
dc.identifier.uri | http://hdl.handle.net/2440/105139 | - |
dc.description.abstract | Aims: High-density lipoproteins (HDL) exert striking anti-inflammatory effects and emerging evidence suggests that they may augment ischaemia-mediated neovascularization. We sought to determine whether HDL conditionally regulates angiogenesis, depending on the pathophysiological context by (i) inhibiting inflammation-induced angiogenesis, but also; (ii) enhancing ischaemia-mediated angiogenesis. Methods and results: Intravenously delivered apolipoprotein (apo) A-I attenuated neovascularization in the murine femoral collar model of inflammation-induced angiogenesis, compared with phosphate-buffered saline infused C57BL6/J mice (58%), P < 0.05. Conversely, apoA-I delivery augmented neovessel formation (75%) and enhanced blood perfusion (45%) in the murine hindlimb ischaemia model, P < 0.05. Reconstituted HDL (rHDL) was tested on key angiogenic cell functions in vitro. rHDL inhibited human coronary artery endothelial cell migration (37.9 and 76.9%), proliferation (15.7 and 40.4%), and tubulogenesis on matrigel (52 and 98.7%) when exposed to two inflammatory stimuli: tumour necrosis factor-α (TNF-α) and macrophage-conditioned media (MCM). In contrast, rHDL significantly augmented hypoxia-stimulated migration (36.9%), proliferation (135%), and tubulogenesis (22.9%), P < 0.05. Western blot and RT–PCR analyses revealed that these divergent actions of rHDL were associated with conditional regulation of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and VEGF receptor 2, which were attenuated in response to TNF-α (40.4, 41.0, and 33.2%) and MCM (72.5, 30.7, and 69.5%), but augmented by rHDL in hypoxia (39.8, 152.6, and 15.7%%), all P < 0.05. Conclusion: HDL differentially regulates angiogenesis dependent upon the pathophysiological setting, characterized by suppression of inflammation-associated angiogenesis, and conversely, by the enhancement of hypoxia-mediated angiogenesis. This has significant implications for therapeutic modulation of neovascularization. | - |
dc.description.statementofresponsibility | Hamish C.G. Prosser, Joanne T.M. Tan, Louise L. Dunn, Sanjay Patel, Laura Z. Vanags, Shisan Bao, Martin K.C. Ng, and Christina A. Bursill | - |
dc.language.iso | en | - |
dc.publisher | Oxford University Press | - |
dc.rights | All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com. | - |
dc.source.uri | http://dx.doi.org/10.1093/cvr/cvt234 | - |
dc.subject | Cells, Cultured | - |
dc.subject | Animals | - |
dc.subject | Mice, Inbred C57BL | - |
dc.subject | Humans | - |
dc.subject | Neovascularization, Pathologic | - |
dc.subject | Vascular Endothelial Growth Factor Receptor-2 | - |
dc.subject | Lipoproteins, HDL | - |
dc.subject | Vascular Endothelial Growth Factor A | - |
dc.subject | Apolipoprotein A-I | - |
dc.subject | Random Allocation | - |
dc.subject | Neovascularization, Physiologic | - |
dc.subject | Male | - |
dc.subject | Hypoxia-Inducible Factor 1, alpha Subunit | - |
dc.title | Multifunctional regulation of angiogenesis by high-density lipoproteins | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1093/cvr/cvt234 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/632512 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/537537 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Bursill, C. [0000-0002-0682-8760] [0000-0003-1087-7781] | - |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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