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Abstract 304: Molecular Mechanisms of Electrically-induced Cardioprotection

Ischemic preconditioning (IPC) is a well-characterized cardioprotective phenomenon involving multiple brief, non-lethal ischemic episodes to the heart. Remote ischemic preconditioning (RIPC) elicits cardioprotection via repetitive ischemia and reperfusion to a distant vascular bed, organ, or limb. A non-ischemic, nociceptive stimulus in distant tissues can result in the most powerful cardioprotection reported - an 80% decrease in infarct size - called remote nociceptor-induced cardioprotection (NIC). Electrically induced cardioprotection via electrical stimulation with electroacupuncture needles (EA) or skin patches (ES) on the abdomen may be a clinically feasible way to induce NIC. A 5 volt, 15 minute electrical stimulus applied as either preconditioning or postconditioning reduces infarct size in a mouse surgical model of myocardial infarction. This study’s objective is to determine the molecular mechanism of electrically-induced NIC. Our previous work shows that IPC requires upregulation and post-transcriptional regulation of heat shock proteins (HSPs), which act in unity to assist in protein folding, repair, and degradation following myocardial injury. However, Western blotting and PCR revealed non-significant changes in HSP mRNA and protein relative to sham, which were inconsistent with the large, significant increases in HSPs observed after IPC. Studies using mice with a genetic deletion of HSP70.1 revealed that this heat shock protein is not required for protection. The transcription factor NF-κB regulates many cardioprotective genes in the heart after IPC, including, but not limited to, heat shock proteins. Based on our work in IPC, we hypothesize that electrical stimulation of the skin is cardioprotective via a unique induction of NF-κB-dependent genes. Pharmacological and genetic inhibition of NF-κB were utilized to evaluate the role of this transcription factor in electrically-induced cardioprotection. Deep sequencing studies are in progress to delineate the presence and quantity of additional transcripts that may be involved in electrically-induced cardioprotection. Future investigations will address the neurobiology of electrically-induced cardioprotection via skin stimulation.