Late onset vascular dysfunction in the R6/1 model of Huntington's disease.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3219311
- author
- 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
- organization
-
- Vascular Physiology (research group)
- Cellular Biomechanics (research group)
- Infection Medicine (BMC)
- Airway Inflammation and Immunology (research group)
- Department of Experimental Medical Science
- Neural Plasticity and Repair (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- publishing date
- 2012-10-29
- type
- Contribution to journal
- publication status
- published
- subject
- in
- European Journal of Pharmacology
- publisher
- Elsevier
- external identifiers
-
- wos:000314616200044
- pmid:23117088
- scopus:84871921332
- pmid:23117088
- 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
- 2016-04-04 08:38:35
- date last changed
- 2022-03-15 08:35:01
@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}}, doi = {{10.1016/j.ejphar.2012.10.026}}, year = {{2012}}, }