Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction

R. J. Hassink, H. Nakajima, H. O. Nakajima, P. A. Doevendans, L. J. Field

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Transgenic mice expressing the dominant interfering p193 protein in cardiomyocytes (MHC-1152stop mice) exhibit an induction of cell cycle activity and altered remodelling after experimental myocardial infarction (MI). Objective: To determine whether the altered remodelling results in improved cardiac function in the MHC-1152stop mice after MI, as compared with non-transgenic mice. Methods: MHC-1152stop mice and non-transgenic littermates were subjected to experimental MI via permanent occlusion of the coronary artery. Infarct size was determined at 24 h and at 4 weeks after MI, and left ventricular pressure-volume measurements were performed at 4 weeks after MI in infarcted and shamoperated animals. Results: Infarct size in MHC-1152stop mice and nontransgenic littermates was not statistically different at 24 h after MI, as measured by tetrazolium staining. Morphometric analysis showed that infarct scar expansion at 4 weeks after MI was reduced by 10% in the MHC-1152stop mice (p<0.05). No differences in cardiac function were detected between sham-operated MHC-1152stop mice and their non-transgenic littermates. However, at 4 weeks after MI, the ventricular isovolumic relaxation time constant (τ) was decreased by 19% (p<0.05), and the slope of the dP/dtmax-EDV relationship was increased 99% (p<0.05), in infarcted MHC-1152stop mice as compared with infarcted non-transgenic littermates. Conclusion: Expression of the dominant interfering p193 transgene results in a decrease in infarct scar expansion and preservation of myocardial function at 4 weeks after MI. Antagonism of p193 activity may represent an important strategy for the treatment of MI.

Original languageEnglish (US)
Pages (from-to)1159-1164
Number of pages6
JournalHeart
Volume95
Issue number14
DOIs
StatePublished - Jul 1 2009

Fingerprint

Transgenes
Myocardial Infarction
Transgenic Mice
Cicatrix
Ventricular Pressure
Cardiac Myocytes
Coronary Vessels
Cell Cycle
Staining and Labeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction. / Hassink, R. J.; Nakajima, H.; Nakajima, H. O.; Doevendans, P. A.; Field, L. J.

In: Heart, Vol. 95, No. 14, 01.07.2009, p. 1159-1164.

Research output: Contribution to journalArticle

Hassink, R. J. ; Nakajima, H. ; Nakajima, H. O. ; Doevendans, P. A. ; Field, L. J. / Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction. In: Heart. 2009 ; Vol. 95, No. 14. pp. 1159-1164.
@article{5c3feaa7d63c4d0bba53426301859338,
title = "Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction",
abstract = "Background: Transgenic mice expressing the dominant interfering p193 protein in cardiomyocytes (MHC-1152stop mice) exhibit an induction of cell cycle activity and altered remodelling after experimental myocardial infarction (MI). Objective: To determine whether the altered remodelling results in improved cardiac function in the MHC-1152stop mice after MI, as compared with non-transgenic mice. Methods: MHC-1152stop mice and non-transgenic littermates were subjected to experimental MI via permanent occlusion of the coronary artery. Infarct size was determined at 24 h and at 4 weeks after MI, and left ventricular pressure-volume measurements were performed at 4 weeks after MI in infarcted and shamoperated animals. Results: Infarct size in MHC-1152stop mice and nontransgenic littermates was not statistically different at 24 h after MI, as measured by tetrazolium staining. Morphometric analysis showed that infarct scar expansion at 4 weeks after MI was reduced by 10{\%} in the MHC-1152stop mice (p<0.05). No differences in cardiac function were detected between sham-operated MHC-1152stop mice and their non-transgenic littermates. However, at 4 weeks after MI, the ventricular isovolumic relaxation time constant (τ) was decreased by 19{\%} (p<0.05), and the slope of the dP/dtmax-EDV relationship was increased 99{\%} (p<0.05), in infarcted MHC-1152stop mice as compared with infarcted non-transgenic littermates. Conclusion: Expression of the dominant interfering p193 transgene results in a decrease in infarct scar expansion and preservation of myocardial function at 4 weeks after MI. Antagonism of p193 activity may represent an important strategy for the treatment of MI.",
author = "Hassink, {R. J.} and H. Nakajima and Nakajima, {H. O.} and Doevendans, {P. A.} and Field, {L. J.}",
year = "2009",
month = "7",
day = "1",
doi = "10.1136/hrt.2008.150128",
language = "English (US)",
volume = "95",
pages = "1159--1164",
journal = "Heart",
issn = "1355-6037",
publisher = "BMJ Publishing Group",
number = "14",

}

TY - JOUR

T1 - Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction

AU - Hassink, R. J.

AU - Nakajima, H.

AU - Nakajima, H. O.

AU - Doevendans, P. A.

AU - Field, L. J.

PY - 2009/7/1

Y1 - 2009/7/1

N2 - Background: Transgenic mice expressing the dominant interfering p193 protein in cardiomyocytes (MHC-1152stop mice) exhibit an induction of cell cycle activity and altered remodelling after experimental myocardial infarction (MI). Objective: To determine whether the altered remodelling results in improved cardiac function in the MHC-1152stop mice after MI, as compared with non-transgenic mice. Methods: MHC-1152stop mice and non-transgenic littermates were subjected to experimental MI via permanent occlusion of the coronary artery. Infarct size was determined at 24 h and at 4 weeks after MI, and left ventricular pressure-volume measurements were performed at 4 weeks after MI in infarcted and shamoperated animals. Results: Infarct size in MHC-1152stop mice and nontransgenic littermates was not statistically different at 24 h after MI, as measured by tetrazolium staining. Morphometric analysis showed that infarct scar expansion at 4 weeks after MI was reduced by 10% in the MHC-1152stop mice (p<0.05). No differences in cardiac function were detected between sham-operated MHC-1152stop mice and their non-transgenic littermates. However, at 4 weeks after MI, the ventricular isovolumic relaxation time constant (τ) was decreased by 19% (p<0.05), and the slope of the dP/dtmax-EDV relationship was increased 99% (p<0.05), in infarcted MHC-1152stop mice as compared with infarcted non-transgenic littermates. Conclusion: Expression of the dominant interfering p193 transgene results in a decrease in infarct scar expansion and preservation of myocardial function at 4 weeks after MI. Antagonism of p193 activity may represent an important strategy for the treatment of MI.

AB - Background: Transgenic mice expressing the dominant interfering p193 protein in cardiomyocytes (MHC-1152stop mice) exhibit an induction of cell cycle activity and altered remodelling after experimental myocardial infarction (MI). Objective: To determine whether the altered remodelling results in improved cardiac function in the MHC-1152stop mice after MI, as compared with non-transgenic mice. Methods: MHC-1152stop mice and non-transgenic littermates were subjected to experimental MI via permanent occlusion of the coronary artery. Infarct size was determined at 24 h and at 4 weeks after MI, and left ventricular pressure-volume measurements were performed at 4 weeks after MI in infarcted and shamoperated animals. Results: Infarct size in MHC-1152stop mice and nontransgenic littermates was not statistically different at 24 h after MI, as measured by tetrazolium staining. Morphometric analysis showed that infarct scar expansion at 4 weeks after MI was reduced by 10% in the MHC-1152stop mice (p<0.05). No differences in cardiac function were detected between sham-operated MHC-1152stop mice and their non-transgenic littermates. However, at 4 weeks after MI, the ventricular isovolumic relaxation time constant (τ) was decreased by 19% (p<0.05), and the slope of the dP/dtmax-EDV relationship was increased 99% (p<0.05), in infarcted MHC-1152stop mice as compared with infarcted non-transgenic littermates. Conclusion: Expression of the dominant interfering p193 transgene results in a decrease in infarct scar expansion and preservation of myocardial function at 4 weeks after MI. Antagonism of p193 activity may represent an important strategy for the treatment of MI.

UR - http://www.scopus.com/inward/record.url?scp=67650077704&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650077704&partnerID=8YFLogxK

U2 - 10.1136/hrt.2008.150128

DO - 10.1136/hrt.2008.150128

M3 - Article

C2 - 19435717

AN - SCOPUS:67650077704

VL - 95

SP - 1159

EP - 1164

JO - Heart

JF - Heart

SN - 1355-6037

IS - 14

ER -