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Late onset vascular dysfunction in the R6/1 model of Huntington's disease.

Rahman, Awahan; Ekman, Mari LU ; Shakirova, Yulia LU ; Andersson, Kristina E LU ; Mörgelin, Matthias LU ; Erjefält, Jonas LU ; Brundin, Patrik LU ; Li, Jia-Yi LU and Swärd, Karl LU (2012) In European Journal of Pharmacology
Abstract
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.... (More)
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. (Less)
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organization
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Contribution to journal
publication status
published
subject
in
European Journal of Pharmacology
publisher
Elsevier
external identifiers
  • wos:000314616200044
  • pmid:23117088
  • scopus:84871921332
ISSN
1879-0712
DOI
10.1016/j.ejphar.2012.10.026
language
English
LU publication?
yes
id
3e0adde2-7aed-4cbc-bb58-cedf50bb50ac (old id 3219311)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23117088?dopt=Abstract
date added to LUP
2012-12-03 11:33:21
date last changed
2017-03-05 04:19:13
@article{3e0adde2-7aed-4cbc-bb58-cedf50bb50ac,
  abstract     = {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.},
  author       = {Rahman, Awahan and Ekman, Mari and Shakirova, Yulia and Andersson, Kristina E and Mörgelin, Matthias and Erjefält, Jonas and Brundin, Patrik and Li, Jia-Yi and Swärd, Karl},
  issn         = {1879-0712},
  language     = {eng},
  month        = {10},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Late onset vascular dysfunction in the R6/1 model of Huntington's disease.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2012.10.026},
  year         = {2012},
}