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https://hdl.handle.net/2440/105139
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Type: | Journal article |
Title: | Multifunctional regulation of angiogenesis by high-density lipoproteins |
Author: | Prosser, H. Tan, J. Dunn, L. Patel, S. Vanags, L. Bao, S. Ng, M. Bursill, C. |
Citation: | Cardiovascular Research, 2014; 101(1):145-154 |
Publisher: | Oxford University Press |
Issue Date: | 2014 |
ISSN: | 0008-6363 1755-3245 |
Statement of Responsibility: | 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 |
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. |
Keywords: | Cells, Cultured Animals Mice, Inbred C57BL Humans Neovascularization, Pathologic Vascular Endothelial Growth Factor Receptor-2 Lipoproteins, HDL Vascular Endothelial Growth Factor A Apolipoprotein A-I Random Allocation Neovascularization, Physiologic Male Hypoxia-Inducible Factor 1, alpha Subunit |
Rights: | All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com. |
DOI: | 10.1093/cvr/cvt234 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/632512 http://purl.org/au-research/grants/nhmrc/537537 |
Published version: | http://dx.doi.org/10.1093/cvr/cvt234 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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