(Circulation. 1997;96:4343-4348.)
© 1997 American Heart Association, Inc.
Articles |
Small Heat Shock Proteins and Protection Against Ischemic Injury in Cardiac Myocytes
From the Department of Medicine, Divisions of Endocrinology and Metabolism (J.L.M., R.M., W.H.D.) and Cardiology (L.L.B.) and Department of Pharmacology (R.H.-D., L.L.B.), University of California, San Diego.
Background Overexpression of the inducible hsp70 protects
against ischemic cardiac damage. However, it is unclear whether
the small heat shock proteins hsp27 and 
B-crystallin protect against
ischemic injury.
Methods and Results Our aim was to examine whether the
overexpression of hsp27 and B-crystallin in neonatal and adult rat
cardiomyocytes would protect against ischemic
injury. Recombinant adenovirus expressing hsp27 or B-crystallin
under the control of the cytomegalovirus promoter was used to infect
cardiac myocytes at high efficiency as assessed by
immunostaining. Overexpression was confirmed by Western
blot analysis. Cardiomyocytes were subjected to simulated
ischemic stress, and survival was estimated through assessment
of lactate dehydrogenase and creatine phosphokinase release. The hsp27
overexpression decreased lactate dehydrogenase release by 45±7.5% in
adult cardiomyocytes but had no effect in the neonatal
cells. In contrast, B-crystallin overexpression was associated with
a decrease in cytosolic enzyme release in both adult (29±6.6%) and
neonatal (32±5.4%) cardiomyocytes. Decreased
endogenous hsp25 with an antisense adenovirus produced a
29±9.9% increase in damage with simulated ischemia.
Overexpression of the inducible hsp70 in adult
cardiomyocytes was associated with a 34±4.6% decrease in
lactate dehydrogenase release and is in line with our previous results
in neonatal cardiomyocytes.
Conclusions The increased expression of hsp27 and B-crystallin
through an adenovirus vector system protects against ischemic
injury in adult cardiomyocytes. Likewise, the
overexpression of B-crystallin protects against ischemic
damage in neonatal cardiomyocytes. Decreasing the high
levels of endogenous hsp25 present in neonatal
cardiomyocytes renders them more susceptible to damage
caused by simulated ischemia.
Key Words: ischemia • adenovirus • myocytes • proteins
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