Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/103244
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kikuchi, R. | - |
dc.contributor.author | Nakamura, K. | - |
dc.contributor.author | MacLauchlan, S. | - |
dc.contributor.author | Ngo, D. | - |
dc.contributor.author | Shimizu, I. | - |
dc.contributor.author | Fuster, J. | - |
dc.contributor.author | Katanasaka, Y. | - |
dc.contributor.author | Yoshida, S. | - |
dc.contributor.author | Qiu, Y. | - |
dc.contributor.author | Yamaguchi, T. | - |
dc.contributor.author | Matsushita, T. | - |
dc.contributor.author | Murohara, T. | - |
dc.contributor.author | Gokce, N. | - |
dc.contributor.author | Bates, D. | - |
dc.contributor.author | Hamburg, N. | - |
dc.contributor.author | Walsh, K. | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | Nature Medicine, 2014; 20(12):1464-1471 | - |
dc.identifier.issn | 1078-8956 | - |
dc.identifier.issn | 1546-170X | - |
dc.identifier.uri | http://hdl.handle.net/2440/103244 | - |
dc.description.abstract | Peripheral artery disease (PAD) generates tissue ischemia through arterial occlusions and insufficient collateral vessel formation. Vascular insufficiency in PAD occurs despite higher circulating levels of vascular endothelial growth factor A (VEGF-A)¹ ², a key regulator of angiogenesis. Here we show that clinical PAD is associated with elevated levels of an antiangiogenic VEGF-A splice isoform (VEGF-A₁₆₅b) and a corresponding reduction in levels of the proangiogenic VEGF-A₁₆₅a splice isoform. In mice, VEGF-A₁₆₅b expression was upregulated by conditions associated with impaired limb revascularization, including leptin deficiency, diet-induced obesity, genetic ablation of the secreted frizzled-related protein 5 (Sfrp5) adipokine and transgenic overexpression of Wnt5a in myeloid cells. In a mouse model of PAD, delivery of VEGF-A₁₆₅b inhibited revascularization of ischemic hind limbs, whereas treatment with an isoform-specific neutralizing antibody reversed impaired revascularization caused by metabolic dysfunction or perturbations in the Wnt5a-Sfrp5 regulatory system. These results indicate that inflammation-driven expression of the antiangiogenic VEGF-A isoform can contribute to impaired collateralization in ischemic cardiovascular disease. | - |
dc.description.statementofresponsibility | Ryosuke Kikuchi, Kazuto Nakamura, Susan MacLauchlan, Doan Thi-Minh Ngo, Ippei Shimizu, Jose Javier Fuster, Yasufumi Katanasaka, Sumiko Yoshida, Yan Qiu, Terry P Yamaguchi, Tadashi Matsushita, Toyoaki Murohara, Noyan Gokce, David O Bates, Naomi M Hamburg, Kenneth Walsh | - |
dc.language.iso | en | - |
dc.publisher | Nature Publishing Group | - |
dc.rights | © 2014 Nature America, Inc. All rights reserved. | - |
dc.source.uri | http://dx.doi.org/10.1038/nm.3703 | - |
dc.subject | Periphery artery disease | - |
dc.title | An antiangiogenic isoform of VEGF-A contributes to impaired vascularization in peripheral artery disease | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1038/nm.3703 | - |
pubs.publication-status | Published | - |
Appears in Collections: | Aurora harvest 3 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.