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Cell, Vol. 98, 555558, September 3, 1999, Copyright 1999 by Cell Press Stress Pathways and Heart Failure Minireview

Summary: Cell, Vol. 98, 555558, September 3, 1999, Copyright 1999 by Cell Press
Stress Pathways and Heart Failure Minireview
thinning of the walls of the ventricular chamber (FigureKenneth R. Chien, M.D., Ph.D.
UCSD--Salk Program in Molecular Medicine 1). Familial hypertrophic cardiomyopathy, which at first
UCSD School of Medicine is not accompanied by chamber dilation, occurs due to
La Jolla, California 92093 mutations affecting proteins in the sarcomere, which
comprises the contractile machinery of heart muscle
(Seidman and Seidman, 1999), while familial dilated car-
The study of complex heart diseases has always been diomyopathy has now been linked to mutations in cy-
a vexing task, akin to solving a 1000-part jigsaw puzzle toskeletal genes (for a list, see Chen and Chien, 1999).
with few obvious connecting pieces. Acquired cardio- In addition, mice harboring muscle-specific mutations in
vascular diseases, such as atherogenesis and heart fail- extra-sarcomeric cytoskeletal proteins display a dilated
ure, arise via the interaction of environmental factors cardiomyopathy phenotype, consistent with a direct role
and genetic susceptibility to produce complicated le- of the cytoskeleton in intrinsic signals for dilated cardio-
sions that cannot be explained by a single gene or path- myopathy. Accordingly, it is now critical to show
way. Distinguishing primary from secondary events, whether these cytoskeletal proteins have a nonspecific
proving causality, and finding the intersecting pieces structural role or a specific signaling role in chamber
has proven a significant challenge. Nevertheless, as evi- dilation.
denced by the pioneering work on the LDL receptor Cytoskeletal Pathways and Dilated Cardiomyopathy
pathway in atherogenesis, genetic-based analysis of rel- The first genetic link between the cytoskeleton and car-


Source: Akabas, Myles - Department of Physiology and Biophysics, Albert Einstein College of Medicine, Yeshiva University


Collections: Biology and Medicine