Document Detail


Potential role of Toll-like receptors in programming of vascular dysfunction.
MedLine Citation:
PMID:  23485061     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The developmental origins of the metabolic syndrome have been established through the consistent observation that small-for-gestational age and large-for-gestational age fetuses have an increased risk for hypertension and related metabolic disorders later in life. These phenotypes have been reproduced in various species subjected to a range of intrauterine insults and ongoing research is directed towards understanding the underlying molecular mechanisms. Current evidence suggests that the creation of a pro-inflammatory and pro-oxidant intrauterine milieu is a common thread among prenatal factors that have an impact upon fetal size. Furthermore, studies demonstrate that a shift in fetal redox status consequent to environmental cues persists after birth and drives the progression of vascular dysfunction and hypertension in postnatal life. TLR (Toll-like receptor) signalling has emerged as a key link between inflammation and oxidative stress and a pathogenic contributor to hypertension, insulin resistance and obesity, in both human patients and animal models of disease. Thus TLR activation and dysregulation of its signalling components represent potential molecular underpinnings of programmed hypertension and related disorders in those subjected to suboptimal intrauterine conditions, yet their contributions to developmental programming remain unexplored. We propose that danger signals mobilized by the placenta or fetal tissues during complicated pregnancy activate the fetal innate immune system through TLRs and thereby potentiate the generation of ROS (reactive oxygen species) and orchestrate fetal adaptive responses, including changes in gene expression, which later translate to vascular dysfunction. Furthermore, we suggest that, after birth, continual activation of TLR signalling propagates vascular oxidative stress and thereby accelerates the advancement of hypertension and heart failure.
Authors:
Jennifer A Thompson; R Clinton Webb
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-03-13
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  125     ISSN:  1470-8736     ISO Abbreviation:  Clin. Sci.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-03-14     Completed Date:  2013-05-02     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  19-25     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Fetal Development
Humans
Hypertension / etiology*,  metabolism
Inflammation / metabolism
Metabolic Syndrome X / etiology*,  metabolism
Oxidative Stress
Reactive Oxygen Species / metabolism
Toll-Like Receptors / metabolism*
Grant Support
ID/Acronym/Agency:
DK-83685/DK/NIDDK NIH HHS; R01 DK083685/DK/NIDDK NIH HHS; R01 HL071138/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 0/Toll-Like Receptors
Comments/Corrections

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


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