Abstract:
:Increased TNFα-mediated JNK signaling in the perivascular adipose tissue (PVAT) may contribute to the pathogenesis of vascular complications in T1DM by reducing adiponectin (Ad) synthesis and therefore impairing Ad-mediated activity in the contiguous blood vessel system. We evaluated whether in vivo treatment with the TNFα blocking antibody infliximab normalized expression of Ad and Ad receptors in various fat depots, and whether this effect correlated with improved endothelial activity and vasodilator function in streptozotocin (STZ)-induced diabetic mice. STZ mice were studied at 1 and 2weeks after diabetes onset, and compared to age-matched infliximab-treated diabetic (I-STZ) and control animals (CTRL) (n=10 each group). In STZ mice, activation of pro-inflammatory JNK signaling was faster in PVAT (P<0.01) than in visceral (VAT), epididymal (EAT) and subcutaneous (SAT) adipose depots, and associated with decreased Ad synthesis and dysregulated AdipoR1/R2 levels. In parallel, activation of JNK in aortic endothelial cells and mesenteric arteries was associated with decreased expression/phosphorylation of eNOS and impaired ACh-mediated vasodilation (P<0.05 vs. CTRL). Treatment with infliximab abrogated JNK activation, ameliorated Ad protein expression, and normalized expression of both AdipoR1 and AdipoR2 in PVAT, concomitantly improving eNOS expression and vessel relaxation in mesenteric arteries from I-STZ mice (P<0.01 vs. STZ). These observations underline the early susceptibility of PVAT to activation of pro-inflammatory JNK signaling, and highlight its potential importance in early vascular changes of T1DM. Further elucidation of the role of PVAT in cardiovascular complications may allow for the design of novel therapeutic strategies directly addressing PVAT pathophysiology.
journal_name
Vascul Pharmacoljournal_title
Vascular pharmacologyauthors
Nacci C,Leo V,De Benedictis L,Potenza MA,Sgarra L,De Salvia MA,Quon MJ,Montagnani Mdoi
10.1016/j.vph.2016.08.007subject
Has Abstractpub_date
2016-12-01 00:00:00pages
83-91eissn
1537-1891issn
1879-3649pii
S1537-1891(16)30165-3journal_volume
87pub_type
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journal_title:Vascular pharmacology
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更新日期:2015-08-01 00:00:00
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doi:10.1016/j.vph.2010.03.002
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pub_type: 杂志文章
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journal_title:Vascular pharmacology
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journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
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journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
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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,评审
doi:10.1016/j.vph.2014.01.003
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journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
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journal_title:Vascular pharmacology
pub_type: 杂志文章
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2016.10.001
更新日期:2016-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/s1537-1891(02)00307-5
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2011.04.001
更新日期:2011-07-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2010.11.001
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/s1537-1891(02)00309-9
更新日期:2003-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.vph.2020.106827
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.2005.03.005
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journal_title:Vascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 杂志文章
doi:10.1016/j.vph.2008.03.004
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journal_title:Vascular pharmacology
pub_type: 杂志文章
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更新日期:2021-02-01 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
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pub_type: 杂志文章,评审
doi:10.1016/s1537-1891(02)00121-0
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pub_type: 杂志文章
doi:10.1016/j.vph.2018.07.001
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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.2012.11.003
更新日期:2013-04-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2005.11.002
更新日期:2006-03-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.vph.2012.02.003
更新日期:2012-05-01 00:00:00
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journal_title:Vascular pharmacology
pub_type: 杂志文章
doi:10.1016/j.vph.2008.01.009
更新日期:2008-04-01 00:00:00