Circulation. 1998;97:1890-1892
(Circulation. 1998;97:1890-1892.)
© 1998 American Heart Association, Inc.
Signaling Hypertrophy
How Many Switches, How Many Wires
Charles J. Homcy, MD
From COR Therapeutics, Inc, South San Francisco, Calif.
Correspondence to Charles J. Homcy, MD, Research and Development, COR Therapeutics, Inc, 256 E Grand Ave, South San Francisco, CA 94080.
Key Words: Editorials • hypertrophy • angiotensin • receptors • signal transduction
Despite the
longstanding appreciation by cardiologists of its fundamental
importance, the hypertrophic process nevertheless remains an enigma.
Key questions have not been answered. What are the outside-in signals
that initiate this process? How many pathways can communicate these
signals? Do they all converge to trigger the same orchestrated
inside-out cardiac response? Cardiac hypertrophy appears to
encompass more than one phenotype, even at the cellular level.
Is there a good form of hypertrophy (a beneficial myocyte
response) versus bad hypertrophy (the dysfunctional
response)? But with the heart, the situation is, of course, even more
complicated. The architecture of this organ is an important determinant
of function; hence, alteration of the normal geometry of the heart as a
consequence of hypertrophy can have important
consequences—again, some worse than others. The
myocardium, particularly in the setting of severe
hypertrophy, can pay a high price in terms of its
requirements for both substrates and O2.
Thus, it is no surprise that cardiologists are always eagerly
awaiting the chance to turn the next page on this story, hoping to find
the answers to the above questions. Over the past 50 years at least,
cardiologists, physiologists, biochemists, pharmacologists, and now
molecular biologists have worked to understand this process, with each
discipline finding, of course, what it is best prepared to recognize.
The molecular signals underlying the genesis of hypertrophy
would be a wonderful prize to garner. How many switches are there? Do
they connect to multiple sets of wires, and where do these wires
terminate? . . . [Full Text of this Article]
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