It is reported that ischemia-reperfusion induces apoptotic cell death in my
ocardium. It is also demonstrated that heat shock protein 70 (HSP70) enhanc
es myocardial tolerance. Therefore, it is hypothesized that HSP70 may play
a role in the attenuation of myocardial apoptosis. To elucidate this goal,
HSP70-overexpressing and control-transfected rat hearts were prepared using
gene transfection by intra-coronary infusion of the hemagglutinating virus
of Japan-liposome.
In vivo experiment Hearts of both groups were subjected to global ischemia,
followed by reperfusion in situ. Shorter recovery time to spontaneous beat
ing (HSP70-transfected vs control-transfected; 46.7 +/- 4.6 vs 67.5 +/- 7.0
s, p = 0.033) and lower serum CPK levels (415 +/- 27 vs 533 +/- 36 IU, p =
0.027) were observed in the HSP70-transfected group. The HSP70-transfected
group also showed a lower percentage of cardiac myocytes positively staine
d by nick end labeling after ischemia-reperfusion (17.5 +/- 4.9 vs 40.0 +/-
5.1 %, p = 0.010).
In vitro experiment Cardiac myocytes isolated from the hearts of both group
s (prepared separately from the in vivo experiment) were subjected to hypox
ia-reoxygenation. Flow cytometry was used to identify the cells that showed
sub-G(1) DNA content as apoptotic cells. Apoptotic cells as a percentage o
f viable cells increased more in the control-transfected group after hypoxi
a-reoxygenation (13.0 +/- 0.77 vs 21.9 +/- 1.18 %, p < 0.0001).
In conclusion, we demonstrated that apoptosis after ischemia-reperfusion wa
s decreased in the HSP70-overexpressin heart in vivo and in vitro, leading
to the suggestion that HSP70 could be associated with the reduction in myoc
ardial apoptosis.