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Perlecan is critical for heart stability

Sasse, Philipp; Malan, Daniela; Fleischmann, Michaela; Roell, Wilhelm; Gustafsson, Erika LU ; Bostani, Toktam; Fan, Yun; Kolbe, Thomas; Breitbach, Martin and Addicks, Klaus, et al. (2008) In Cardiovascular Research 80(3). p.435-444
Abstract
Perlecan is a heparansulfate proteoglycan found in basement membranes, cartilage, and several mesenchymal tissues that form during development, tumour growth, and tissue repair. Loss-of-function mutations in the perlecan gene in mice are associated with embryonic lethality caused primarily by cardiac abnormalities probably due to hemopericards. The aim of the present study was to investigate the mechanism underlying the early embryonic lethality and the pathophysiological relevance of perlecan for heart function. Perlecan-deficient murine embryonic stem cells were used to investigate the myofibrillar network and the electrophysiological properties of single cardiomyocytes. The mechanical stability of the developing perlecan-deficient mouse... (More)
Perlecan is a heparansulfate proteoglycan found in basement membranes, cartilage, and several mesenchymal tissues that form during development, tumour growth, and tissue repair. Loss-of-function mutations in the perlecan gene in mice are associated with embryonic lethality caused primarily by cardiac abnormalities probably due to hemopericards. The aim of the present study was to investigate the mechanism underlying the early embryonic lethality and the pathophysiological relevance of perlecan for heart function. Perlecan-deficient murine embryonic stem cells were used to investigate the myofibrillar network and the electrophysiological properties of single cardiomyocytes. The mechanical stability of the developing perlecan-deficient mouse hearts was analysed by microinjecting fluorescent-labelled dextran. Maturation and formation of basement membranes and cell-cell contacts were investigated by electron microscopy, immunohistochemistry, and western blotting. Sarcomere formation and cellular functional properties were unaffected in perlecan-deficient cardiomyocytes. However, the intraventricular dye injection experiments revealed mechanical instability of the early embryonic mouse heart muscle wall before embryonic day 10.5 (E10.5). Accordingly, perlecan-null embryonic hearts contained lower amounts of the critical basement membrane components, collagen IV and laminins. Furthermore, basement membranes were absent in perlecan-null cardiomoycytes whereas adherens junctions formed and matured around E9.5. Infarcted hearts from perlecan heterozygous mice displayed reduced heart function when compared with wild-type hearts. We propose that perlecan plays an important role in maintaining the integrity during cardiac development and is important for heart function in the adult heart after injury. (Less)
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Cardiovascular Research
volume
80
issue
3
pages
435 - 444
publisher
Elsevier
external identifiers
  • wos:000260973500016
  • scopus:56549087641
ISSN
1755-3245
DOI
10.1093/cvr/cvn225
language
English
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yes
id
0c6f6d8b-401f-4ef8-98ce-0a112848309c (old id 1283536)
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2009-02-10 10:43:29
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2017-01-01 04:32:24
@article{0c6f6d8b-401f-4ef8-98ce-0a112848309c,
  abstract     = {Perlecan is a heparansulfate proteoglycan found in basement membranes, cartilage, and several mesenchymal tissues that form during development, tumour growth, and tissue repair. Loss-of-function mutations in the perlecan gene in mice are associated with embryonic lethality caused primarily by cardiac abnormalities probably due to hemopericards. The aim of the present study was to investigate the mechanism underlying the early embryonic lethality and the pathophysiological relevance of perlecan for heart function. Perlecan-deficient murine embryonic stem cells were used to investigate the myofibrillar network and the electrophysiological properties of single cardiomyocytes. The mechanical stability of the developing perlecan-deficient mouse hearts was analysed by microinjecting fluorescent-labelled dextran. Maturation and formation of basement membranes and cell-cell contacts were investigated by electron microscopy, immunohistochemistry, and western blotting. Sarcomere formation and cellular functional properties were unaffected in perlecan-deficient cardiomyocytes. However, the intraventricular dye injection experiments revealed mechanical instability of the early embryonic mouse heart muscle wall before embryonic day 10.5 (E10.5). Accordingly, perlecan-null embryonic hearts contained lower amounts of the critical basement membrane components, collagen IV and laminins. Furthermore, basement membranes were absent in perlecan-null cardiomoycytes whereas adherens junctions formed and matured around E9.5. Infarcted hearts from perlecan heterozygous mice displayed reduced heart function when compared with wild-type hearts. We propose that perlecan plays an important role in maintaining the integrity during cardiac development and is important for heart function in the adult heart after injury.},
  author       = {Sasse, Philipp and Malan, Daniela and Fleischmann, Michaela and Roell, Wilhelm and Gustafsson, Erika and Bostani, Toktam and Fan, Yun and Kolbe, Thomas and Breitbach, Martin and Addicks, Klaus and Welz, Armin and Brem, Gottfried and Hescheler, Juergen and Aszodi, Attila and Costell, Mercedes and Bloch, Wilhelm and Fleischmann, Bernd K.},
  issn         = {1755-3245},
  language     = {eng},
  number       = {3},
  pages        = {435--444},
  publisher    = {Elsevier},
  series       = {Cardiovascular Research},
  title        = {Perlecan is critical for heart stability},
  url          = {http://dx.doi.org/10.1093/cvr/cvn225},
  volume       = {80},
  year         = {2008},
}