Abstract:
:Ischemia/Reperfusion injury and hemolysis are characterized by erythrocyte lysis and release of free heme into the microcirculation. Following substantial erythrocyte lysis, heme overwhelms circulatory heme-binding protein networks rapidly forming hemin, the oxidized form of iron protoporphyrin IX. Hemin's role in modulating inflammatory responses in microvascular endothelium (MVEC) remains ill-defined. We studied the impact of hemin exposure on human MVEC interleukin-8 (IL-8) expression. Hemin significantly up-regulated MVEC IL-8 secretion and was associated with cellular iron loading. Hemin-induced IL-8 up-regulation was significantly attenuated by increasing environmental serum concentrations. As well, hemin-induced IL-8 secretion was significantly reduced in a concentration-dependent fashion following pyrrolidine dithiocarbamate exposure, suggesting that induction occurred via an oxidant-sensitive mechanism. Interestingly, transfection studies revealed that oxidant-driven transcription factors NF-kappaB and AP-1 played no role in hemin-induced IL-8 transcription. In studies employing actinomycin D, hemin was found to dramatically lengthen IL-8 mRNA half-life. Of major importance in the current report was the finding that hypoxia inducible factor-1 (HIF-1), a powerful transcription factor mediating tissue responses to hypoxia, potently regulated hemin-induced IL-8 secretion in human MVEC. Activation of HIF-1 via the prolyl hydroxylase inhibitor dimethyloxalylglycine attenuated hemin-induced IL-8 secretion. These studies were confirmed via DNA-directed siRNA silencing of HIF-1alpha. In conclusion, hemin induces a serum protein-sensitive pro-inflammatory phenotype in MVEC via an oxidant-sensitive mechanism that is powerfully regulated by HIF-1.
journal_name
Microvasc Resjournal_title
Microvascular researchauthors
Natarajan R,Fisher BJ,Fowler AA 3rddoi
10.1016/j.mvr.2007.01.002subject
Has Abstractpub_date
2007-05-01 00:00:00pages
163-72issue
3eissn
0026-2862issn
1095-9319pii
S0026-2862(07)00015-5journal_volume
73pub_type
杂志文章abstract::The size of hyaluronan in lymph and gastrocnemius muscle was measured to test the hypothesis that reperfusion of ischemic skeletal muscle leads to hyaluronan depolymerization. Prenodal lymph was collected from the gastrocnemius muscle in anesthetized rabbits. Hyaluronan size was measured using a combination of agarose...
journal_title:Microvascular research
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1998.2142
更新日期:1999-05-01 00:00:00
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journal_title:Microvascular research
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1993.1060
更新日期:1993-11-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2013.03.007
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journal_title:Microvascular research
pub_type: 杂志文章,评审
doi:10.1016/j.mvr.2013.02.009
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pub_type: 杂志文章,评审
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(83)90050-x
更新日期:1983-07-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1999.2208
更新日期:2000-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0026-2862(86)90036-1
更新日期:1986-03-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(84)90054-2
更新日期:1984-03-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2015.09.003
更新日期:2016-01-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1996.0029
更新日期:1996-05-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(86)90021-x
更新日期:1986-05-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2012.07.006
更新日期:2012-11-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/0026-2862(90)90008-f
更新日期:1990-07-01 00:00:00
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doi:10.1016/j.mvr.2018.03.012
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2010.02.005
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2005.04.007
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2010.01.004
更新日期:2010-03-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2007.06.009
更新日期:2008-03-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2009.05.006
更新日期:2009-09-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.2000.2279
更新日期:2000-11-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2014.02.008
更新日期:2014-05-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1006/mvre.1999.2177
更新日期:1999-11-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2014.10.006
更新日期:2015-01-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2011.11.005
更新日期:2012-03-01 00:00:00
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journal_title:Microvascular research
pub_type: 杂志文章
doi:10.1016/j.mvr.2006.03.001
更新日期:2006-05-01 00:00:00