The Heat Shock Paradox and Cardiac Myocytes

Abstract

The induction of the heat shock response is accepted to be a protective response, reducing injury and improving cell survival. However, when inflammation precedes heat shock there is an unexpected increase in injury, known as the heat shock paradox, which is hypothesized to be a mechanism underlying multi-organ dysfunction. We hypothesized that the heat shock paradox would occur in adult cardiac myocytes and that heat shock factor (HSF)1 would contribute to injury. Heat shock (HS) at 42°C and TNF (10 ng/ml) were used as the HS and the inflammatory insult, respectively. The combination of TNF followed by HS (TNF/HS) caused the greatest amount of apoptosis in adult rat cardiac myocytes. TNF/HS resulted in an increase in heat shock protein (HSP) 60, compared to untreated cells, those receiving HS/TNF, or TNF alone. There was no increase in heme oxygenase 1 in any of the groups. HSP72 increased in all the groups, with the greatest levels with TNF/HS. NFκB activation was greatest with TNF/HS. Pretreatment with a DNA binding decoy for HSF1 prevented the increase in HSPs and decreased apoptosis in all groups. However, the increase in iNOS, seen in all treatment groups, was unaffected by the HSF1 binding decoy. We conclude that the heat shock paradox occurs in adult cardiac myocytes, that HSP60 is increased as part of the heat shock paradox, and that HSF1 activation contributes to injury.

Heat Shock Protein 25-Enriched Plasma Transfusion Preconditions the Heart against Doxorubicin-Induced Dilated Cardiomyopathy in Mice

“…However, if Hsp25 expression is induced after injury (via HSF-1 activation in response to Dox-induced oxidative stress), it is cytotoxic and aggravates apoptosis in the heart (Vedam et al, 2010). In support of these findings, recent studies by the Knowlton group have demonstrated that TNF-␣ injury was worsened by HSF-1 activation induced by heat stress after injury (Kobba et al, 2011). Taken together, the accumulated data indicate that overexpression of eHsp25 by any combined therapy during the treatment of cancer using Dox might result in the suppression of cardiomyopathy.…”

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“…This finding is consistent with a recent report that HSP32/HO-1 was still induced by heat shock in the presence of an Hsf-1 inhibitor in cardiac myocytes. 27 …”

Remote ischemic conditioning: Short-term effects on rat liver ischemic-reperfusion injury

“…Hasonló eredmények-ről olvashatunk szíven [32], agyon [33] és vesén [34] végzett kísérletek esetében is. A HSP-72 szerepe való-színűleg igen szerteágazó, feltételezhetjük, hogy az ischaemia-reperfúzió, illetve a különböző kezelések hatására létrejövő celluláris védelmi mechanizmusok részt-vevője [35,36].…”