(Circulation. 1999;99:334-337.)
© 1999 American Heart Association, Inc.
Editorial |
ß-Protein Kinase C and Hypertrophic Signaling in Human Heart Failure
From the Division of Cardiology and Research Service, Veterans Affairs Medical Center, and the Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco.
Correspondence to Paul C. Simpson, MD, VAMC 111-C-8, 4150 Clement St, San Francisco, CA 94121. E-mail simpson.paul_c@sanfrancisco.va.gov
Key Words: Editorials • heart failure • enzymes
In this issue of Circulation, Bowling et al1 present important data on protein kinase C (PKC) in human heart failure. PKC is a candidate rate-limiting molecular switch in what has come to be known as "hypertrophic signaling," the molecular mechanisms whereby surface and nuclear receptors and their intracellular transducers convert mechanical and soluble growth stimuli into the end product of a bigger cardiac myocyte. Cardiac myocyte hypertrophy is an essential chronic adaptation but is believed to become maladaptive in the so-called "transition from hypertrophy to failure." Thus, hypertrophic signaling has become a research area of intense interest, with the hope that targeting specific signaling molecules by drugs or even gene therapy might be useful in heart failure. This editorial summarizes the present study in the context of recent data on PKC, particularly the ß-isoform of PKC, and considers some unresolved issues and future directions. Recent editorials in this journal have presented variations on the general theme of hypertrophic signaling.2 3 4
Bowling et al1 studied PKC proteins, mRNAs,
and activity in a dozen explanted hearts with end-stage dilated
cardiomyopathy, both ischemic and
idiopathic, and a similar number of nonfailing control hearts. Using
left ventricular free wall samples from failing hearts,
they showed by immunoblot that 2
Ca2+-sensitive PKC isoform proteins, 
and ß
(both the ß1 and ß2
forms), are substantially elevated, by 40% to 70%, in particulate or
"membrane" fractions. Furthermore, the - and ß-PKC proteins
are increased in cardiac myocytes by immunostaining in
tissue sections, and ß1- and
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