PMID- 10591032
OWN - NLM
STAT- MEDLINE
DCOM- 19991228
LR  - 20190831
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 31
IP  - 11
DP  - 1999 Nov
TI  - The absence of desmin leads to cardiomyocyte hypertrophy and cardiac dilation
      with compromised systolic function.
PG  - 2063-76
AB  - Desmin is the muscle-specific member of the intermediate filament family of
      cytoskeletal proteins, expressed both in striated and smooth muscle tissues. In
      mature striated muscle fibers, the desmin filament lattice surrounds the Z-discs,
      interconnects them to each other and links the entire contractile apparatus to
      the sarcolemmal cytoskeleton, cytoplasmic organelles and the nucleus. There have 
      been increasing reports of human cardiomyopathies associated with abnormal
      accumulation and aggregation of desmin filaments. Recently identified desmin
      mutations in humans suffering from skeletal muscle myopathy and cardiomyopathy
      suggest that these diseases might arise as a consequence of impaired function of 
      desmin filaments. Previous generation of desmin null mice in our laboratory
      demonstrated that the absence of desmin results in myocyte ultrastructural
      defects and myocyte cell death leading to fibrosis and calcification of the
      myocardium. However, the effects that these defects have on cardiac function were
      not addressed. To further our understanding of desmin function in vivo, and in
      order to address the direct involvement of desmin in cardiomyopathy, we
      investigated the effect of the absence of desmin on myocardial mass, myocyte size
      and shape, changes in gene expression and cardiac systolic and diastolic function
      in mice. Morphometric characterization of isolated cardiomyocytes demonstrated a 
      24% increase in cell volume in the desmin null mice, solely due to an increase in
      transverse section area, suggesting for the first time that mice lacking the
      intermediate filament protein desmin develop concentric cardiomyocyte
      hypertrophy. This type of hypertrophy was accompanied by induction of embryonic
      gene expression and later by ventricular dilatation, and compromised systolic
      function. These results demonstrate that desmin is essential for normal cardiac
      function, and they suggest that the absence of an intact desmin filament system, 
      rather than accumulation of the protein, may be responsible for the pathology
      seen in some of the desmin associated cardiomyopathies.
FAU - Milner, D J
AU  - Milner DJ
AD  - Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030,
      USA.
FAU - Taffet, G E
AU  - Taffet GE
FAU - Wang, X
AU  - Wang X
FAU - Pham, T
AU  - Pham T
FAU - Tamura, T
AU  - Tamura T
FAU - Hartley, C
AU  - Hartley C
FAU - Gerdes, A M
AU  - Gerdes AM
FAU - Capetanaki, Y
AU  - Capetanaki Y
LA  - eng
GR  - AG13251/AG/NIA NIH HHS/United States
GR  - AR 39617-09/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Desmin)
SB  - IM
MH  - Animals
MH  - Cardiomyopathy, Dilated/genetics/pathology/*physiopathology
MH  - Cardiomyopathy, Hypertrophic/genetics/pathology/*physiopathology
MH  - Chimera
MH  - Desmin/*deficiency/genetics/*physiology
MH  - Exercise Test
MH  - Gene Expression Regulation
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocardium/pathology
MH  - Systole/genetics/*physiology
EDAT- 1999/12/11 00:00
MHDA- 1999/12/11 00:01
CRDT- 1999/12/11 00:00
PHST- 1999/12/11 00:00 [pubmed]
PHST- 1999/12/11 00:01 [medline]
PHST- 1999/12/11 00:00 [entrez]
AID - S0022282899910374 [pii]
AID - 10.1006/jmcc.1999.1037 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 1999 Nov;31(11):2063-76. doi: 10.1006/jmcc.1999.1037.