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Hearts from mice lacking desmin have a myopathy with impaired active force generation and unaltered wall compliance.

Balogh, Johanna LU ; Merisckay, M; Li, Z; Paulin, D and Arner, Anders LU (2002) In Cardiovascular Research 53(2). p.439-450
Abstract
OBJECTIVE: Desmin intermediate filaments are key structures in the cytoskeleton of cardiac muscle. Since they are associated with Z-discs and intercalated discs, they may have a role in sarcomere alignment or force transmission. We have explored the mechanical function of the desmin filaments in the cardiac wall by comparing desmin-deficient (Des-/-) and wild-type (Des+/+) mice. METHODS: The Langendorff technique was used to examine the contractility of the whole heart. Rate of force generation, Ca(2+)-sensitivity and force per cross-sectional area were measured in skinned ventricle muscle preparations. RESULTS: Des-/- mice have a cardiomyopathy with increased heart weight. Diastolic pressure was increased at all filling volumes in the... (More)
OBJECTIVE: Desmin intermediate filaments are key structures in the cytoskeleton of cardiac muscle. Since they are associated with Z-discs and intercalated discs, they may have a role in sarcomere alignment or force transmission. We have explored the mechanical function of the desmin filaments in the cardiac wall by comparing desmin-deficient (Des-/-) and wild-type (Des+/+) mice. METHODS: The Langendorff technique was used to examine the contractility of the whole heart. Rate of force generation, Ca(2+)-sensitivity and force per cross-sectional area were measured in skinned ventricle muscle preparations. RESULTS: Des-/- mice have a cardiomyopathy with increased heart weight. Diastolic pressure was increased at all filling volumes in the Des-/- group. Since passive wall stress (i.e. force per area) was unchanged, the alteration in diastolic pressure is a consequence of the thicker ventricle wall. Developed pressure, rate of pressure increase and developed wall stress were significantly reduced, suggesting that active force generation of the contractile apparatus is reduced in Des-/-. Concentrations of actin and myosin in the ventricle were unaltered. Measurements in skinned muscle preparations showed a lower active force development with unaltered Ca(2+)-sensitivity and rate of tension development. CONCLUSION: It is suggested that the intermediate filaments have a role in active force generation of cardiac muscle, possibly by supporting sarcomere alignment or force transmission. The desmin filaments do not contribute the passive elasticity of the ventricle wall. Des-/- mice provide a model for genetic cardiomyopathy where the main factor contributing to altered cardiac performance is a decrease in active force generation, possibly in combination with a loss of functional contractile units. (Less)
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published
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keywords
Myosins/analysis, Perfusion, Support, Non-U.S. Gov't, Inbred C57BL, Mice, Intermediate Filaments/metabolism, In Vitro, Actins/analysis, Calcium/metabolism, Animal, Myocardium/metabolism, Myocardial Contraction/*physiology, Transgenic, Desmin/genetics/metabolism/*physiology, Female, Heart Diseases/genetics/*physiopathology
in
Cardiovascular Research
volume
53
issue
2
pages
439 - 450
publisher
Elsevier
external identifiers
  • pmid:11827695
  • wos:000175038600021
  • scopus:0036165896
ISSN
1755-3245
DOI
10.1016/S0008-6363(01)00500-4
language
English
LU publication?
yes
id
d59ec056-f42a-4684-a833-fdd31f3cd447 (old id 106186)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11827695&dopt=Abstract
date added to LUP
2007-07-10 09:52:14
date last changed
2017-07-09 03:47:05
@article{d59ec056-f42a-4684-a833-fdd31f3cd447,
  abstract     = {OBJECTIVE: Desmin intermediate filaments are key structures in the cytoskeleton of cardiac muscle. Since they are associated with Z-discs and intercalated discs, they may have a role in sarcomere alignment or force transmission. We have explored the mechanical function of the desmin filaments in the cardiac wall by comparing desmin-deficient (Des-/-) and wild-type (Des+/+) mice. METHODS: The Langendorff technique was used to examine the contractility of the whole heart. Rate of force generation, Ca(2+)-sensitivity and force per cross-sectional area were measured in skinned ventricle muscle preparations. RESULTS: Des-/- mice have a cardiomyopathy with increased heart weight. Diastolic pressure was increased at all filling volumes in the Des-/- group. Since passive wall stress (i.e. force per area) was unchanged, the alteration in diastolic pressure is a consequence of the thicker ventricle wall. Developed pressure, rate of pressure increase and developed wall stress were significantly reduced, suggesting that active force generation of the contractile apparatus is reduced in Des-/-. Concentrations of actin and myosin in the ventricle were unaltered. Measurements in skinned muscle preparations showed a lower active force development with unaltered Ca(2+)-sensitivity and rate of tension development. CONCLUSION: It is suggested that the intermediate filaments have a role in active force generation of cardiac muscle, possibly by supporting sarcomere alignment or force transmission. The desmin filaments do not contribute the passive elasticity of the ventricle wall. Des-/- mice provide a model for genetic cardiomyopathy where the main factor contributing to altered cardiac performance is a decrease in active force generation, possibly in combination with a loss of functional contractile units.},
  author       = {Balogh, Johanna and Merisckay, M and Li, Z and Paulin, D and Arner, Anders},
  issn         = {1755-3245},
  keyword      = {Myosins/analysis,Perfusion,Support,Non-U.S. Gov't,Inbred C57BL,Mice,Intermediate Filaments/metabolism,In Vitro,Actins/analysis,Calcium/metabolism,Animal,Myocardium/metabolism,Myocardial Contraction/*physiology,Transgenic,Desmin/genetics/metabolism/*physiology,Female,Heart Diseases/genetics/*physiopathology},
  language     = {eng},
  number       = {2},
  pages        = {439--450},
  publisher    = {Elsevier},
  series       = {Cardiovascular Research},
  title        = {Hearts from mice lacking desmin have a myopathy with impaired active force generation and unaltered wall compliance.},
  url          = {http://dx.doi.org/10.1016/S0008-6363(01)00500-4},
  volume       = {53},
  year         = {2002},
}