Abstract:
:Angiostatin is an angiogenesis inhibitor in part generated by and released from platelets. Since platelets upon thrombus formation can give rise to areas of hypoxia, we investigated the effects of angiostatin on endothelial cell migration and apoptosis during hypoxia. Human microvascular endothelial cells (HMVEC-L) were exposed to angiostatin under normoxic or hypoxic conditions. Apoptosis was measured by flow-cytometry. HMVEC-L migration was studied using a modified Boyden Chamber assay, in which migration is MMP-dependent. MMP-2, MMP-14, and VEGF levels were measured using immunoblot, Q-PCR and ELISA. During hypoxia HMVEC-L were protected from angiostatin-induced apoptosis due to increased hypoxia-induced VEGF expression. However, MMP-dependent migration of HMVEC-L was inhibited by angiostatin under hypoxic but not normoxic conditions. Angiostatin decreased MMP-2 at the gene and protein levels only in HMVEC-L exposed to hypoxia. A similar result was obtained for MMP-14. Higher angiostatin concentrations, as would be seen during thrombosis, induced HMVEC-L apoptosis, which was not rescued by VEGF. Under hypoxic conditions angiostatin's primary anti-angiogenic mechanism is likely inhibition of endothelial cell MMP-dependent endothelial cell migration. Only at higher concentrations does angiostatin induce endothelial cell death. This study identifies a novel angiostatin anti-angiogenesis mechanism that is only triggered under pathological-like conditions.
journal_name
Vascul Pharmacoljournal_title
Vascular pharmacologyauthors
Radziwon-Balicka A,Ramer C,Moncada de la Rosa C,Zielnik-Drabik B,Jurasz Pdoi
10.1016/j.vph.2012.11.003subject
Has Abstractpub_date
2013-04-01 00:00:00pages
280-91issue
4eissn
1537-1891issn
1879-3649pii
S1537-1891(12)00200-5journal_volume
58pub_type
杂志文章abstract::Venous and arterial walls are responsive to sympathetic system and circulating substances, nevertheless, very few is known about the venous blood flow regulation simultaneously to arterial vascular beds. In this study, we compared the venous and arterial blood flow regulation in visceral and muscular beds upon injecti...
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2015.03.006
更新日期:2015-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-01-01 00:00:00
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journal_title:Vascular pharmacology
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doi:10.1016/j.vph.2015.02.001
更新日期:2015-04-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2016.05.007
更新日期:2016-07-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2005.08.031
更新日期:2006-10-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2005.09.006
更新日期:2006-01-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2012.12.004
更新日期:2013-04-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2012.12.001
更新日期:2013-03-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2007.08.001
更新日期:2007-11-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2010.09.001
更新日期:2010-11-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2011.06.005
更新日期:2011-11-01 00:00:00
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更新日期:2020-12-17 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2006.10.011
更新日期:2007-04-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2006.09.005
更新日期:2007-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:2019-10-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2015.10.006
更新日期:2016-04-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2008.02.002
更新日期:2008-04-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2020.106822
更新日期:2020-11-21 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2014.08.001
更新日期:2014-11-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2005.02.012
更新日期:2005-08-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2006.04.002
更新日期:2006-08-01 00:00:00