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Late onset vascular dysfunction in the R6/1 model of Huntington's disease.
MedLine Citation:
PMID:  23117088     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Huntington's disease is a neurodegenerative disorder that also gives raise to widespread changes in peripheral organs and tissues. We tested the hypothesis that vascular dysfunction may occur in Huntington's disease by studying R6/1 mice which express exon 1 of the mutant huntingtin gene. We assessed arterial function in R6/1 and wild type (WT) mice using myography. Arterial contractility was largely unaltered in R6/1 arteries at 15 and 32 weeks of age. By 40 weeks, contractility was impaired irrespective of which vasoconstrictor we tested. Endothelium-dependent relaxation was not affected, and we observed no changes in arterial geometry or expression of contractile proteins, such as myosin regulatory light chains or smooth muscle α-actin. The frequency of calcium oscillations in R6/1 arterial smooth muscle cells was higher than in WT control tissue, whereas myosin phosphorylation was unaltered. Impairment of force by the mitochondrial inhibitors cyanide and rotenone was less pronounced in R6/1 than in WT arteries and mitochondria were enlarged, in keeping with an effect related to altered mitochondrial function. Our results reveal that arteries in the R6/1 model of Huntington's disease exhibit an age-dependent impairment of contractility and that they depend less on mitochondrial function when they contract.
Authors:
Awahan Rahman; Mari Ekman; Yulia Shakirova; Kristina E Andersson; Matthias Mörgelin; Jonas S Erjefält; Patrik Brundin; Jia-Yi Li; Karl Swärd
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-29
Journal Detail:
Title:  European journal of pharmacology     Volume:  -     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-11-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Section for Cell and Tissue Biology, Department of Experimental Medical Science, Lund University BMC D12 Sweden. Electronic address: Awahan.Reheman@ki.se.
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