Heat acclimation–mediated cross‐tolerance in cardioprotection

Heat acclimation (AC) is an evolutionarily conserved feature allowing adjustment to persistent changes in ambient temperature. The mechanisms underlying acclimation involve a continuum of physiologic changes, determined by temperature-adaptive shifts in gene expression. The AC heart generates greater pressure at lower O2 consumption, but at the expense of contractile velocity, and renders cytoprotection to a wide range of stressors (cross-tolerance) via greater cytoprotective protein reserves, faster post-injury molecular dynamic response, and post-translational modifications. A greater abundance of HSP70 and HIF-1alpha and its metabolic targeted genes (both nuclear and mitochondrial) are among the cytoprotective changes that occur. The cytoprotection profile provides a dual protective strategy--a constitutive availability of cytoprotective proteins without a need for de novo protein synthesis, together with an "alerted system" responding rapidly upon insult. Hence, cross-tolerance is achieved via activation of "on-call" constitutive cytoprotection shared by all stressors, together with organ-specific functional remodeling and stress-specific cross-talk.