| Inducible and myocyte-specific inhibition of PKCalpha enhances cardiac contractility and protects against infarction-induced heart failure. | |
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MedLine Citation:
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PMID: 17921332 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mice null for the gene encoding protein kinase Calpha (Prkca), or mice treated with pharmacologic inhibitors of the PKCalpha/beta/gamma isoforms, show an augmentation in cardiac contractility that appears to be cardioprotective. However, it remains uncertain if PKCalpha itself functions in a myocyte autonomous manner to affect cardioprotection in vivo. Here we generated cardiac myocyte-specific transgenic mice using a tetracycline-inducible system to permit controlled expression of dominant negative PKCalpha in the heart. Consistent with the proposed function of PKCalpha, induction of dominant negative PKCalpha expression in the adult heart enhanced baseline cardiac contractility. This increase in cardiac contractility was associated with a partial protection from long-term decompensation and secondary dilated cardiomyopathy after myocardial infarction injury. Similarly, Prkca null mice were also partially protected from infarction-induced heart failure, although the area of infarction injury was identical to controls. Thus, myocyte autonomous inhibition of PKCalpha protects the adult heart from decompensation and dilated cardiomyopathy after infarction injury in association with a primary enhancement in contractility. |
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Authors:
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Michael Hambleton; Allen York; Michelle A Sargent; Robert A Kaiser; John N Lorenz; Jeffrey Robbins; Jeffery D Molkentin |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-10-05 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 293 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2007 Dec |
Date Detail:
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Created Date: 2007-12-06 Completed Date: 2008-01-31 Revised Date: 2012-10-09 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H3768-71 Citation Subset: IM |
Affiliation:
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Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiomegaly / enzymology, etiology, physiopathology, prevention & control* Disease Models, Animal Heart Failure / enzymology, etiology, physiopathology, prevention & control* Mice Mice, Knockout Mice, Transgenic Myocardial Contraction* / genetics Myocardial Infarction / complications, enzymology, pathology, physiopathology* Myocardium / enzymology*, pathology Protein Kinase C-alpha / deficiency, genetics, metabolism* Time Factors Ventricular Dysfunction / enzymology, etiology, physiopathology, prevention & control* |
| Grant Support | |
ID/Acronym/Agency:
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P01 HL069779-06A10003/HL/NHLBI NIH HHS; P50 HL077101-050004/HL/NHLBI NIH HHS; R01 HL060562/HL/NHLBI NIH HHS; R01 HL060562-11/HL/NHLBI NIH HHS; R01 HL062927-10A1/HL/NHLBI NIH HHS; R01 HL081104-04/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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EC 2.7.11.13/Prkca protein, mouse; EC 2.7.11.13/Protein Kinase C-alpha |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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