Abstract:
:Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are cytoplasmic adaptor proteins of the TNF/interleukin (IL)-1/Toll-like receptor superfamily. Ligands of this family such as TNFα, CD40L, and IL-1β promote chronic inflammatory processes such as atherosclerosis and restenosis, the latter being a common adverse reaction after vascular interventions. We previously reported overexpression of TRAF5 in murine and human atheromata and TRAF5-dependent proinflammatory functions in vitro. However, the role of TRAF5 in restenosis remains unsettled. To evaluate whether TRAF5 affects neointima formation, TRAF5-/-LDLR-/- and TRAF5+/+LDLR-/- mice consuming a high cholesterol diet (HCD) received wire-induced injury of the carotid artery. After 28 days, TRAF5-deficient mice showed a 45% decrease in neointimal area formation compared with TRAF5-compentent mice. Furthermore, neointimal vascular smooth muscle cells (vSMC) and macrophages decreased whereas collagen increased in TRAF5-deficient mice. Mechanistically, the latter expressed lower transcript levels of the matrix metalloproteinases 2 and 9, both instrumental in extracellular matrix degradation and vSMC mobilization. Additionally, TRAF5-specific siRNA interference rendered murine vSMC less proliferative upon CD40L stimulation. In accordance with these findings, fewer vSMC isolated from TRAF5-deficient aortas were in a proliferative state as assessed by Ki67 and cyclin B1 expression. In conclusion, TRAF5 deficiency mitigates neointima formation in mice, likely through a TRAF5-dependent decrease in vSMC proliferation.
journal_name
J Vasc Resjournal_title
Journal of vascular researchauthors
Willecke F,Rupprecht B,Gissler MC,Pfeiffer K,Anto-Michel N,Stachon P,Wolf D,Hilgendorf I,Hoppe N,Bode C,Zirlik Adoi
10.1159/000501615subject
Has Abstractpub_date
2019-01-01 00:00:00pages
308-319issue
6eissn
1018-1172issn
1423-0135pii
000501615journal_volume
56pub_type
杂志文章abstract::This study was designed to establish the in vitro pharmacological responses of rat middle cerebral arteries (MCA), and also their susceptibility to overnight cold storage at 4 degrees C. MCAs were harvested from rats and pharmacological responses were studied using a Mulvany myograph. Responses to prostaglandin F2 alp...
journal_title:Journal of vascular research
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更新日期:2006-01-01 00:00:00
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journal_title:Journal of vascular research
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journal_title:Journal of vascular research
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更新日期:2013-01-01 00:00:00
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journal_title:Journal of vascular research
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journal_title:Journal of vascular research
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journal_title:Journal of vascular research
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doi:10.1159/000076126
更新日期:2004-01-01 00:00:00
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journal_title:Journal of vascular research
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journal_title:Journal of vascular research
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doi:10.1159/000124283
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journal_title:Journal of vascular research
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pub_type: 杂志文章,评审
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更新日期:2011-01-01 00:00:00
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journal_title:Journal of vascular research
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更新日期:1999-09-01 00:00:00
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journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000025733
更新日期:2000-05-01 00:00:00
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journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000158987
更新日期:1993-05-01 00:00:00
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