Abstract | BACKGROUND: METHODS AND RESULTS: Control (MR(flox/flox), MR(flox/wt)) and MR(MLCCre) mice underwent coronary artery ligation. MR ablation had no detectable baseline effect on cardiac morphology and function. The progressive left ventricular chamber enlargement and functional deterioration in infarcted control mice, detected by echocardiography and conductance catheter analysis during the 8-week observation period, were substantially attenuated in MR(MLCCre) mice. Chronically infarcted MR(MLCCre) mice displayed attenuated pulmonary edema, reduced cardiac hypertrophy, increased capillary density, and reduced accumulation of extracellular matrix proteins in the surviving left ventricular myocardium. Moreover, cardiomyocyte-specific MR ablation prevented the increases in myocardial and mitochondrial O(2)(·-) production and upregulation of the NADPH oxidase subunits Nox2 and Nox4. At 7 days, MR(MLCCre) mice exhibited enhanced infarct neovessel formation and collagen structural organization associated with reduced infarct expansion. Mechanistically, cardiomyocytes lacking MR displayed accelerated stress-induced activation and subsequent suppression of nuclear factor-κB and reduced apoptosis early after myocardial infarction. CONCLUSION: Cardiomyocyte-specific MR deficiency improved infarct healing and prevented progressive adverse cardiac remodeling, contractile dysfunction, and molecular alterations in ischemic heart failure, highlighting the importance of cardiomyocyte MR for heart failure development and progression.
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Authors | Daniela Fraccarollo, Stefan Berger, Paolo Galuppo, Susanne Kneitz, Lutz Hein, Günther Schütz, Stefan Frantz, Georg Ertl, Johann Bauersachs |
Journal | Circulation
(Circulation)
Vol. 123
Issue 4
Pg. 400-8
(Feb 01 2011)
ISSN: 1524-4539 [Electronic] United States |
PMID | 21242479
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Membrane Glycoproteins
- NF-kappa B
- Receptors, Mineralocorticoid
- Superoxides
- Cybb protein, mouse
- NADPH Oxidase 2
- NADPH Oxidase 4
- NADPH Oxidases
- Nox4 protein, mouse
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Topics |
- Animals
- Apoptosis
- Cardiomegaly
(metabolism, physiopathology)
- Cells, Cultured
- Coronary Vessels
(metabolism, physiopathology)
- Female
- Gene Deletion
- Male
- Membrane Glycoproteins
(metabolism)
- Mice
- Mice, Transgenic
- Myocardial Infarction
(genetics, metabolism, physiopathology)
- Myocytes, Cardiac
(metabolism, physiology)
- NADPH Oxidase 2
- NADPH Oxidase 4
- NADPH Oxidases
(metabolism)
- NF-kappa B
(metabolism)
- Neovascularization, Physiologic
- Pulmonary Edema
(metabolism, physiopathology)
- Receptors, Mineralocorticoid
(genetics, metabolism, physiology)
- Superoxides
(metabolism)
- Up-Regulation
- Ventricular Remodeling
(genetics, physiology)
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