Document Detail

Inducible and myocyte-specific inhibition of PKCalpha enhances cardiac contractility and protects against infarction-induced heart failure.
MedLine Citation:
PMID:  17921332     Owner:  NLM     Status:  MEDLINE    
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.
Michael Hambleton; Allen York; Michelle A Sargent; Robert A Kaiser; John N Lorenz; Jeffrey Robbins; Jeffery D Molkentin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-10-05
Journal Detail:
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:
Created Date:  2007-12-06     Completed Date:  2008-01-31     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H3768-71     Citation Subset:  IM    
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MeSH Terms
Cardiomegaly / enzymology,  etiology,  physiopathology,  prevention & control*
Disease Models, Animal
Heart Failure / enzymology,  etiology,  physiopathology,  prevention & control*
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
P01 HL069779/HL/NHLBI NIH HHS; P01 HL069779-06A10003/HL/NHLBI NIH HHS; P50 HL077101/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/HL/NHLBI NIH HHS; R01 HL062927-10A1/HL/NHLBI NIH HHS; R01 HL081104/HL/NHLBI NIH HHS; R01 HL081104-04/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
EC protein, mouse; EC Kinase C-alpha

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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