RELATIVE INDUCTION OF HEAT-SHOCK-PROTEIN IN CORONARY ENDOTHELIAL-CELLS AND CARDIOMYOCYTES - IMPLICATIONS FOR MYOCARDIAL PROTECTION

Objectives: Induction of the 70 kd heat shock protein in the heart is known to exert a protective effect against postischemic mechanical and endothelial dysfunction. However, the exact site of induction and the mechanisms involved remain unknown. The aim of this study was to inve stigate the relative capacity of endothelial and myocardial cells to e xpress the 70 kd heat shock protein in response to heat stress, as wel l as their significance. Methods: (1) Postischemic recovery of cardiac mechanical and endothelial function was studied in isolated rat heart s with and without endothelial denudation with saponin, (2) Semiquanti tative determination of induction of 70 kd heat shock protein by Weste rn immunoblotting was performed in the whole cardiac homogenate, in is olated cardiac myocytes, and in coronary endothelial cells. (3) Immuno cytochemistry was used to visualize the distribution of induction of 7 0 kd heat shock protein in both cell types, Results: Postischemic reco very (percent preischemic value a standard error of the mean) of cardi ac output in hearts from heat-stressed animals was significantly impro ved (66.7 +/- 6.9 vs 44.5 +/- 4.5 in the control group, p < 0.01), In heat-stressed hearts treated with saponin no improvement in the recove ry of cardiac output was noted (44.7 +/- 6.9 in heat-stressed hearts v s 38.0 +/- 4.0 in heat-stressed, saponin-treated hearts, p = not signi ficant). Endothelial function (as assessed by the vasodilatory respons e to the endothelium-dependent vasodilator 5-hydroxytryptamine) improv ed from 31.0 +/- 5.2 in the control group to 65.8 +/- 7.1 in heat-stre ssed hearts (p < 0.02 vs control) and dropped to -1.9 +/- 3.8 in heat- stressed hearts treated with saponin. Immunocytochemistry showed that only sections of hearts from heat-treated rats showed a strong specifi c reaction with heat shock protein antibody, The positive staining was seen in endothelial cells. Induction of 70 kd heat shock protein cont ent in the whole cardiac homogenate from heat-stressed rats as measure d by Western immunoblotting was 5.2 +/- 1.9 (vs 0.0 in non-heat-stress ed rats, p < 0.0001) and dropped to 0.0 in heat-stressed hearts treate d with saponin, The tentative amount of 70 kd heat shock protein was 1 8.1 +/- 7.8 in isolated endothelial cells from heat-stressed hearts an d 2.3 +/- 2.3 in isolated cardiac myocytes (p < 0.01 vs endothelial ce lls). Conclusions: Coronary endothelial cells are the main site of ind uction of 70 kd heat shock protein in the heart and appear to contribu te to the protective effects of heat stress on the recovery of mechani cal and endothelial function.