Cardiac-specific overexpression of catalase identifies hydrogen peroxide-dependent and-independent phases of myocardial remodeling and prevents the progression to overt heart failure in Gαq-overexpressing transgenic mice

Fuzhong Qin, Shannon Lennon-Edwards, Steve Lancel, Andreia Biolo, Deborah A. Siwik, David R. Pimentel, Gerald W. Dorn, Yujian Kang, Wilson S. Colucci

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: Although it seems that reactive oxygen species contribute to chronic myocardial remodeling, questions remain about (1) the specific types of reactive oxygen species involved, (2) the role of reactive oxygen species in mediating specific cellular events, and (3) the cause-and-effect relationship between myocardial reactive oxygen species and the progression to heart failure. Transgenic mice with myocyte-specific overexpression of Gαq develop a dilated cardiomyopathy that progresses to heart failure. We used this model to examine the role of H 2 O 2 in mediating myocardial remodeling and the progression to failure. Methods and Results: In Gαq myocardium, markers of oxidative stress were increased at 4 weeks and increased further at 20 weeks. Gαq mice were crossbred with transgenic mice having myocyte-specific overexpression of catalase. At 4 weeks of age, left ventricular end-diastolic dimension was increased and left ventricular fractional shortening decreased in Gαq mice and deteriorated further through 20 weeks. In Gαq mice, myocardial catalase overexpression had no effect on left ventricular end-diastolic dimension or fractional shortening at 4 weeks but prevented the subsequent deterioration in both. In Gαq mice, myocyte hypertrophy; myocyte apoptosis; interstitial fibrosis; and the progression to overt heart failure, as reflected by lung congestion and exercise intolerance, were prevented by catalase overexpression. Conclusion: In Gαq mice, myocyte-specific overexpression of catalase had no effect on the initial phenotype of left ventricular dilation and contractile dysfunction but prevented the subsequent progressive remodeling phase leading to heart failure. Catalase prevented the cellular hallmarks of adverse remodeling (myocyte hypertrophy, myocyte apoptosis, and interstitial fibrosis) and the progression to overt heart failure. Thus, H 2 O 2 , associated oxidant pathways, or both play a critical role in adverse myocardial remodeling and the progression to failure.

Original languageEnglish (US)
Pages (from-to)306-313
Number of pages8
JournalCirculation: Heart Failure
Volume3
Issue number2
DOIs
StatePublished - Mar 1 2010

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Catalase
Muscle Cells
Hydrogen Peroxide
Transgenic Mice
Heart Failure
Reactive Oxygen Species
Hypertrophy
Fibrosis
Apoptosis
Dilated Cardiomyopathy
Oxidants
Dilatation
Myocardium
Oxidative Stress
Phenotype
Lung

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Cardiac-specific overexpression of catalase identifies hydrogen peroxide-dependent and-independent phases of myocardial remodeling and prevents the progression to overt heart failure in Gαq-overexpressing transgenic mice. / Qin, Fuzhong; Lennon-Edwards, Shannon; Lancel, Steve; Biolo, Andreia; Siwik, Deborah A.; Pimentel, David R.; Dorn, Gerald W.; Kang, Yujian; Colucci, Wilson S.

In: Circulation: Heart Failure, Vol. 3, No. 2, 01.03.2010, p. 306-313.

Research output: Contribution to journalArticle

Qin, Fuzhong ; Lennon-Edwards, Shannon ; Lancel, Steve ; Biolo, Andreia ; Siwik, Deborah A. ; Pimentel, David R. ; Dorn, Gerald W. ; Kang, Yujian ; Colucci, Wilson S. / Cardiac-specific overexpression of catalase identifies hydrogen peroxide-dependent and-independent phases of myocardial remodeling and prevents the progression to overt heart failure in Gαq-overexpressing transgenic mice. In: Circulation: Heart Failure. 2010 ; Vol. 3, No. 2. pp. 306-313.
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abstract = "Background: Although it seems that reactive oxygen species contribute to chronic myocardial remodeling, questions remain about (1) the specific types of reactive oxygen species involved, (2) the role of reactive oxygen species in mediating specific cellular events, and (3) the cause-and-effect relationship between myocardial reactive oxygen species and the progression to heart failure. Transgenic mice with myocyte-specific overexpression of Gαq develop a dilated cardiomyopathy that progresses to heart failure. We used this model to examine the role of H 2 O 2 in mediating myocardial remodeling and the progression to failure. Methods and Results: In Gαq myocardium, markers of oxidative stress were increased at 4 weeks and increased further at 20 weeks. Gαq mice were crossbred with transgenic mice having myocyte-specific overexpression of catalase. At 4 weeks of age, left ventricular end-diastolic dimension was increased and left ventricular fractional shortening decreased in Gαq mice and deteriorated further through 20 weeks. In Gαq mice, myocardial catalase overexpression had no effect on left ventricular end-diastolic dimension or fractional shortening at 4 weeks but prevented the subsequent deterioration in both. In Gαq mice, myocyte hypertrophy; myocyte apoptosis; interstitial fibrosis; and the progression to overt heart failure, as reflected by lung congestion and exercise intolerance, were prevented by catalase overexpression. Conclusion: In Gαq mice, myocyte-specific overexpression of catalase had no effect on the initial phenotype of left ventricular dilation and contractile dysfunction but prevented the subsequent progressive remodeling phase leading to heart failure. Catalase prevented the cellular hallmarks of adverse remodeling (myocyte hypertrophy, myocyte apoptosis, and interstitial fibrosis) and the progression to overt heart failure. Thus, H 2 O 2 , associated oxidant pathways, or both play a critical role in adverse myocardial remodeling and the progression to failure.",
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T1 - Cardiac-specific overexpression of catalase identifies hydrogen peroxide-dependent and-independent phases of myocardial remodeling and prevents the progression to overt heart failure in Gαq-overexpressing transgenic mice

AU - Qin, Fuzhong

AU - Lennon-Edwards, Shannon

AU - Lancel, Steve

AU - Biolo, Andreia

AU - Siwik, Deborah A.

AU - Pimentel, David R.

AU - Dorn, Gerald W.

AU - Kang, Yujian

AU - Colucci, Wilson S.

PY - 2010/3/1

Y1 - 2010/3/1

N2 - Background: Although it seems that reactive oxygen species contribute to chronic myocardial remodeling, questions remain about (1) the specific types of reactive oxygen species involved, (2) the role of reactive oxygen species in mediating specific cellular events, and (3) the cause-and-effect relationship between myocardial reactive oxygen species and the progression to heart failure. Transgenic mice with myocyte-specific overexpression of Gαq develop a dilated cardiomyopathy that progresses to heart failure. We used this model to examine the role of H 2 O 2 in mediating myocardial remodeling and the progression to failure. Methods and Results: In Gαq myocardium, markers of oxidative stress were increased at 4 weeks and increased further at 20 weeks. Gαq mice were crossbred with transgenic mice having myocyte-specific overexpression of catalase. At 4 weeks of age, left ventricular end-diastolic dimension was increased and left ventricular fractional shortening decreased in Gαq mice and deteriorated further through 20 weeks. In Gαq mice, myocardial catalase overexpression had no effect on left ventricular end-diastolic dimension or fractional shortening at 4 weeks but prevented the subsequent deterioration in both. In Gαq mice, myocyte hypertrophy; myocyte apoptosis; interstitial fibrosis; and the progression to overt heart failure, as reflected by lung congestion and exercise intolerance, were prevented by catalase overexpression. Conclusion: In Gαq mice, myocyte-specific overexpression of catalase had no effect on the initial phenotype of left ventricular dilation and contractile dysfunction but prevented the subsequent progressive remodeling phase leading to heart failure. Catalase prevented the cellular hallmarks of adverse remodeling (myocyte hypertrophy, myocyte apoptosis, and interstitial fibrosis) and the progression to overt heart failure. Thus, H 2 O 2 , associated oxidant pathways, or both play a critical role in adverse myocardial remodeling and the progression to failure.

AB - Background: Although it seems that reactive oxygen species contribute to chronic myocardial remodeling, questions remain about (1) the specific types of reactive oxygen species involved, (2) the role of reactive oxygen species in mediating specific cellular events, and (3) the cause-and-effect relationship between myocardial reactive oxygen species and the progression to heart failure. Transgenic mice with myocyte-specific overexpression of Gαq develop a dilated cardiomyopathy that progresses to heart failure. We used this model to examine the role of H 2 O 2 in mediating myocardial remodeling and the progression to failure. Methods and Results: In Gαq myocardium, markers of oxidative stress were increased at 4 weeks and increased further at 20 weeks. Gαq mice were crossbred with transgenic mice having myocyte-specific overexpression of catalase. At 4 weeks of age, left ventricular end-diastolic dimension was increased and left ventricular fractional shortening decreased in Gαq mice and deteriorated further through 20 weeks. In Gαq mice, myocardial catalase overexpression had no effect on left ventricular end-diastolic dimension or fractional shortening at 4 weeks but prevented the subsequent deterioration in both. In Gαq mice, myocyte hypertrophy; myocyte apoptosis; interstitial fibrosis; and the progression to overt heart failure, as reflected by lung congestion and exercise intolerance, were prevented by catalase overexpression. Conclusion: In Gαq mice, myocyte-specific overexpression of catalase had no effect on the initial phenotype of left ventricular dilation and contractile dysfunction but prevented the subsequent progressive remodeling phase leading to heart failure. Catalase prevented the cellular hallmarks of adverse remodeling (myocyte hypertrophy, myocyte apoptosis, and interstitial fibrosis) and the progression to overt heart failure. Thus, H 2 O 2 , associated oxidant pathways, or both play a critical role in adverse myocardial remodeling and the progression to failure.

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