Hibernation and plasma from hibernating animals modulate the cardioprotective delta opioid system

Abstract

Our goal is to harness the protective effects of mammalian hibernation to prevent and to treat cardiovascular disease (CVD). CVD is among the leading causes of morbidity and mortality in the United States. The specific objective of this study was to determine the effect of hibernation on the cardiac delta opioid system, and to determine the mechanisms by which plasma from hibernating woodchucks (HWP) is cardioprotective. Hearts were collected from summer woodchucks and squirrels, and from animals at defined times in the hibernation cycle. Tissues were analyzed by real‐time PCR for gene expression and by Western blot analysis for protein levels. Immunofluorescence microscopy was used to determine the effects of HWP on cellular localization of the delta opioid receptor (DOR). Hibernation induced dynamic changes in cardiac expression of opioid genes, and altered protein levels of the delta opioid precursor proenkephalin and of DOR. HWP increased localization of DOR to the plasma membrane of primary human vascular cells, suggesting that mobilization of DOR to cell surfaces may contribute to cardioprotection. These data support a role for delta opioids and their receptor in the hibernation phenotype, and provide insights that will further the development of therapies based on the natural protective processes of hibernation. Funded by the Department of Emergency Medicine, The University of Iowa.