Interstitial remodeling in beta1-adrenergic receptor transgenic mice
U. Seeland, S. Selejan, S. Engelhardt, P. Muller, M. Lohse, and M. Bohm. Basic Res Cardiol, 102 (2):
183-93(March 2007)Seeland, Ute Selejan, Simina Engelhardt, Stefan Muller, Patrick Lohse,
Martin J Bohm, Michael Research Support, Non-U.S. Gov't Germany Basic
research in cardiology Basic Res Cardiol. 2007 Mar;102(2):183-93.
Epub 2006 Nov 24..
Abstract
BACKGROUND: Inhibition of proteolytic MMP activity could be a therapeutic
approach to prevent ventricular dilatation by diminishing collagen
matrix turnover and interstitial fibrosis. We investigated the time-course
of MMP/TIMP activity during transition from hypertrophy to ventricular
dilatation in transgenic mice with myocyte overexpression of the
human beta1-adrenergic receptor (beta1TG). These beta1TG mice were
studied at 3 (normal function), 5 (hypertrophy) and 12 (ventricular
dilatation) months of age compared to age-matched controls (WT).
METHODS: Picro Sirius red staining and real-time PCR were performed
for total collagen and for collagen type I and III quantification,
respectively. MMP-activity assays (zymography), immunoblotting and
real-time PCR experiments were done for gelatinase- (MMP-2, -9),
collagenase- (MMP-1, -13), membrane-type MMP- (MT1- MMP; MMP-14)
and TIMP expression measurements. To investigate beta1-integrin activity,
integrin-linked kinase (ILK) expression was measured by immunoblotting.
RESULTS: Compared to WT with normal cardiac function, interstitial
collagen type I and III mRNA and protein expression increased 3.6-fold
in beta1TG at 5 months of age with moderate fibrosis and cardiomyocyte
hypertrophy and 17-fold in beta1TG at 12 months of age with severe
fibrosis and ventricular dilatation. Protein expression of the collagenases
MMP-1 and -13 as well as the gelatinase proMMP-2 increased in the
beta1TG group with cardiac hypertrophy. Maximal activity of the gelatinase
MMP-2 (3.5-fold vs.WT) was measured in beta1TG at 12 months of age
with severe fibrosis and ventricular dilatation, accompanied by coexpression
of MT1- MMP (3.8-fold vs.WT) colocalized to the cell membranes. CONCLUSION:
These data provide evidence that sympathetic overactivation can trigger
interstitial matrix remodeling and fibrosis by induction of MMP/TIMP
activity. In particular gelatinolytic MMP-2 activity accompanies
ventricular dilatation and the development of heart failure.
Seeland, Ute Selejan, Simina Engelhardt, Stefan Muller, Patrick Lohse,
Martin J Bohm, Michael Research Support, Non-U.S. Gov't Germany Basic
research in cardiology Basic Res Cardiol. 2007 Mar;102(2):183-93.
Epub 2006 Nov 24.
%0 Journal Article
%1 Seeland2007
%A Seeland, U.
%A Selejan, S.
%A Engelhardt, S.
%A Muller, P.
%A Lohse, M. J.
%A Bohm, M.
%D 2007
%J Basic Res Cardiol
%K Aging/metabolism Animals Cardiac/*metabolism Collagen/metabolism Collagenases/metabolism Extracellular Hypertrophy, Inhibitor Kinases/metabolism Left Matrix Matrix/metabolism Metalloproteinases/*metabolism Mice Myocytes, Protein-Serine-Threonine Tissue Transgenic Ventricular/*metabolism beta-1/*metabolism of Receptor Adrenergic
%N 2
%P 183-93
%T Interstitial remodeling in beta1-adrenergic receptor transgenic mice
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17122889
%V 102
%X BACKGROUND: Inhibition of proteolytic MMP activity could be a therapeutic
approach to prevent ventricular dilatation by diminishing collagen
matrix turnover and interstitial fibrosis. We investigated the time-course
of MMP/TIMP activity during transition from hypertrophy to ventricular
dilatation in transgenic mice with myocyte overexpression of the
human beta1-adrenergic receptor (beta1TG). These beta1TG mice were
studied at 3 (normal function), 5 (hypertrophy) and 12 (ventricular
dilatation) months of age compared to age-matched controls (WT).
METHODS: Picro Sirius red staining and real-time PCR were performed
for total collagen and for collagen type I and III quantification,
respectively. MMP-activity assays (zymography), immunoblotting and
real-time PCR experiments were done for gelatinase- (MMP-2, -9),
collagenase- (MMP-1, -13), membrane-type MMP- (MT1- MMP; MMP-14)
and TIMP expression measurements. To investigate beta1-integrin activity,
integrin-linked kinase (ILK) expression was measured by immunoblotting.
RESULTS: Compared to WT with normal cardiac function, interstitial
collagen type I and III mRNA and protein expression increased 3.6-fold
in beta1TG at 5 months of age with moderate fibrosis and cardiomyocyte
hypertrophy and 17-fold in beta1TG at 12 months of age with severe
fibrosis and ventricular dilatation. Protein expression of the collagenases
MMP-1 and -13 as well as the gelatinase proMMP-2 increased in the
beta1TG group with cardiac hypertrophy. Maximal activity of the gelatinase
MMP-2 (3.5-fold vs.WT) was measured in beta1TG at 12 months of age
with severe fibrosis and ventricular dilatation, accompanied by coexpression
of MT1- MMP (3.8-fold vs.WT) colocalized to the cell membranes. CONCLUSION:
These data provide evidence that sympathetic overactivation can trigger
interstitial matrix remodeling and fibrosis by induction of MMP/TIMP
activity. In particular gelatinolytic MMP-2 activity accompanies
ventricular dilatation and the development of heart failure.
@article{Seeland2007,
abstract = {BACKGROUND: Inhibition of proteolytic MMP activity could be a therapeutic
approach to prevent ventricular dilatation by diminishing collagen
matrix turnover and interstitial fibrosis. We investigated the time-course
of MMP/TIMP activity during transition from hypertrophy to ventricular
dilatation in transgenic mice with myocyte overexpression of the
human beta1-adrenergic receptor (beta1TG). These beta1TG mice were
studied at 3 (normal function), 5 (hypertrophy) and 12 (ventricular
dilatation) months of age compared to age-matched controls (WT).
METHODS: Picro Sirius red staining and real-time PCR were performed
for total collagen and for collagen type I and III quantification,
respectively. MMP-activity assays (zymography), immunoblotting and
real-time PCR experiments were done for gelatinase- (MMP-2, -9),
collagenase- (MMP-1, -13), membrane-type MMP- (MT1- MMP; MMP-14)
and TIMP expression measurements. To investigate beta1-integrin activity,
integrin-linked kinase (ILK) expression was measured by immunoblotting.
RESULTS: Compared to WT with normal cardiac function, interstitial
collagen type I and III mRNA and protein expression increased 3.6-fold
in beta1TG at 5 months of age with moderate fibrosis and cardiomyocyte
hypertrophy and 17-fold in beta1TG at 12 months of age with severe
fibrosis and ventricular dilatation. Protein expression of the collagenases
MMP-1 and -13 as well as the gelatinase proMMP-2 increased in the
beta1TG group with cardiac hypertrophy. Maximal activity of the gelatinase
MMP-2 (3.5-fold vs.WT) was measured in beta1TG at 12 months of age
with severe fibrosis and ventricular dilatation, accompanied by coexpression
of MT1- MMP (3.8-fold vs.WT) colocalized to the cell membranes. CONCLUSION:
These data provide evidence that sympathetic overactivation can trigger
interstitial matrix remodeling and fibrosis by induction of MMP/TIMP
activity. In particular gelatinolytic MMP-2 activity accompanies
ventricular dilatation and the development of heart failure.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Seeland, U. and Selejan, S. and Engelhardt, S. and Muller, P. and Lohse, M. J. and Bohm, M.},
biburl = {https://www.bibsonomy.org/bibtex/2248b29873c27615a157104dac5fa3235/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {0794aa212249ee24428b3688e735c14c},
intrahash = {248b29873c27615a157104dac5fa3235},
issn = {0300-8428 (Print) 0300-8428 (Linking)},
journal = {Basic Res Cardiol},
keywords = {Aging/metabolism Animals Cardiac/*metabolism Collagen/metabolism Collagenases/metabolism Extracellular Hypertrophy, Inhibitor Kinases/metabolism Left Matrix Matrix/metabolism Metalloproteinases/*metabolism Mice Myocytes, Protein-Serine-Threonine Tissue Transgenic Ventricular/*metabolism beta-1/*metabolism of Receptor Adrenergic},
month = Mar,
note = {Seeland, Ute Selejan, Simina Engelhardt, Stefan Muller, Patrick Lohse,
Martin J Bohm, Michael Research Support, Non-U.S. Gov't Germany Basic
research in cardiology Basic Res Cardiol. 2007 Mar;102(2):183-93.
Epub 2006 Nov 24.},
number = 2,
pages = {183-93},
shorttitle = {Interstitial remodeling in beta1-adrenergic receptor transgenic mice},
timestamp = {2010-12-14T18:22:42.000+0100},
title = {Interstitial remodeling in beta1-adrenergic receptor transgenic mice},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17122889},
volume = 102,
year = 2007
}