Gp130-Dependent Cytokines May Prevent Heart Failure

	April 19, 1999 - Cytokines that operate via 
gp130 pathways have a crucial role in preventing 
onset of heart failure, say researchers. Dr. Hisao 
Hirota, of the University of California at San Diego
and colleagues at the University of Cologne in 
Germany bred mice with heart tissue that lacked the 
gp130 cytokine receptor. Using miniaturized echo and
cardiac cath, they confirmed that these mice had 
normal heart structure and function.
	In these mice and control mice, Dr. Hirota's 
team surgically caused heart enlargement. The 
experimental mice showed no gp130 activation and 2 
days later, echo showed that left ventricle end-
diastolic size had significantly increased.
	Within 7 days after the procedure, more than
90% of the experimental mice had died vs only 30% of
the control mice. On tissue examination, the 
research team found ventricular enlargement in the 
experimental mice.
	The rapid onset of heart failure in the 
expereimental mice was associated with a "massive 
induction" of stress-activated cell death. 3-4 days 
after the researchers induced heart hypertrophy, 
cell death was more extensive in experimental mice 
than in control mice, affecting at least 1/3 of 
heart cells.
	"These studies identify heart cell death 
as a critical point in the transition between 
heart enlargement and heart failure," the authors 
write in the April 16th issue of Cell. They add that 
gp130 is an "essential part" of the heart cell 
survival pathway.
	Dr. Hirota's group concludes that "the 
inhibition of heart cell death is now a valid 
target for the development of new drugs for heart 
failure."

Cell 1999;97:189-198