Document Detail


Role of NF-kappaB in flow-induced vascular remodeling.
MedLine Citation:
PMID:  19320561     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Vascular remodeling associated with increased blood flow involves reactive oxygen species (ROS)-dependent activation of matrix metalloproteinases (MMPs). To investigate the potential role of NF-kappaB in this process, human umbilical vein endothelial cells were subjected to different flow conditions during a 24-h period. Normal (15 dynes/cm(2)) and high (30 dynes/cm(2)) shear stress induced IkappaBalpha degradation and NF-kappaB p65 phosphorylation, and activated MMP-2 and MMP-9. These effects were blunted in cells incubated with the NF-kappaB inhibitor pyrrolidine dithio-carbamate (PDTC). In mice, creation of a carotid artery-jugular vein arteriovenous fistula (AVF) increased carotid blood flow sixfold, triggering the increase in carotid diameter from 459 +/- 8 microm (before AVF) to 531 +/- 13 and 669 +/- 21 microm (7 and 21 days after AVF). ROS production and NF-kappaB activity were enhanced in fistulated carotids, but only the latter was blocked by PDTC, although PDTC blocked ROS production in vitro. In PDTC-treated mice, changes in carotid caliber and shear stress matched controls at 7 days, but carotids enlarged only marginally thereafter, reaching only 578 +/- 8 microm at 21 days (p < 0.01 vs. untreated). Similarly, both MMP-9 expression and activity were abrogated by PDTC at 3 weeks. Hence, induction of NF-kappaB by shear stress contributes to MMP induction and allows long-term flow-induced vascular enlargement.
Authors:
Yves Castier; Bhama Ramkhelawon; Stéphanie Riou; Alain Tedgui; Stephanie Lehoux
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  11     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-12-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1641-9     Citation Subset:  IM    
Affiliation:
Parts Cardiovascular Research Center, Inserm U970, HEGP, Paris, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Increased prevalence of insulin resistance in patients with differentiated thyroid carcinoma.
Next Document:  Hemodynamic forces, vascular oxidative stress and regulation of BMP-2/4 expression.